Outer coat
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24
RETPAHC
The ocular lens is located immediately behind the iris and is sus- The external surface of the sclera is covered by a delicate episcleral
pended from the ciliary body via zonular fibres (see Fig. 42.1). Smooth lamina of loose fibrovascular tissue, which contains sparse blood vessels
muscles within the ciliary body regulate the tension exerted on the and is in contact with the inner surface of the fascial sheath of the
elastic lens and hence determine its shape, thereby adjusting the focus eyeball. Anteriorly, the external scleral surface is covered by conjunctiva,
of the eye in the process of accommodation. The iris, which does not which is reflected on to it from the posterior surfaces of the eyelids. The
allow the transmission of light due to a heavily pigmented posterior scleral internal surface adjacent to the choroid is attached to it by a
surface, also contains smooth muscle, allowing it to regulate the size of delicate fibrous layer, the suprachoroid lamina, which contains numer-
the pupillary aperture. ous fibroblasts and melanocytes. Anteriorly, the inner sclera is attached
The iris and lens separate the eye into three chambers. The largest, to the ciliary body by the lamina supraciliaris. Posteriorly, the sclera is
the vitreous chamber, is filled with the gel-like vitreous humour, and pierced by the optic nerve. Here, the outer half of the sclera turns back
lies posterior to the lens, comprising about two-thirds of the volume of to become continuous with the dura mater, while the inner half is
the eye (see Fig. 42.1). The spaces between the lens and iris, and the modified to form a perforated plate, the lamina cribrosa sclerae. The
iris and cornea, are, respectively, the posterior and anterior chambers optic nerve fascicles pass through these minute orifices, while the
of the eye. Both are filled with aqueous humour, which is produced by central retinal artery and vein pass through a larger, central aperture.
the epithelium of the ciliary body, travels through the pupil, circulates The lamina cribrosa sclerae is the weakest part of the sclera and bulges


in the anterior chamber and is drained principally through the canal of outwards (a cupped disc) when intraocular pressure is raised chroni-
Schlemm at the iridocorneal filtration angle. Aqueous humour provides cally, as in glaucoma.
metabolic support to the avascular lens and cornea. Like the cornea, the scleral stroma is composed mainly of densely
The sole purpose of the eyes and their associated structures within packed collagen embedded in a matrix of proteoglycans, which are
the bony orbit is to form a good image on a healthy retina. The photo- mixed with occasional elastic fibres and fibroblasts. However, in con-
receptors of the retina transduce the optical radiation into neurobio- trast to the cornea, scleral collagen fibrils show a large variation in
logical activity and other cells within the retina then begin to process diameter and spacing, and the lamellae branch and interlace exten-
the output of the photoreceptors. The retinal signal is transferred via sively. This arrangement of fibres results in increased light scatter, which
the optic nerve, along the visual pathway (see Fig. 42.32) to various is responsible for the opaque, dull-white appearance of the sclera, and
regions within the brain, where further processing results in visual also imparts a high tensile strength to the sclera to resist the pull of the
perception. extraocular muscles and contain the intraocular pressure. Collagen fibre
bundles are arranged circumferentially around the optic disc and the
orifices of the lamina cribrosa. The fibres of the tendons of the recti
OUTER COAT
intersect scleral fibres at right angles at their attachments, and then
interlace deeper in the sclera. Collagen fibres of the scleral spur are
The fibrous outer coat of the eye consists of the opaque posterior sclera orientated in a circular fashion, and there is an increased incidence of
and the transparent anterior cornea. Together they form a semi-elastic elastic fibres here (Figs 42.2–42.3A). Although the sclera acts as a
protective capsule enclosing the eye, which, when made turgid by conduit for blood vessels, scleral vessels are few and mainly disposed
intraocular pressure, determines the optical geometry of the eye and in the episcleral lamina, especially close to the limbus. Its nerve supply


ensures its shape is not distorted when it moves. The sclera also provides is surprisingly rich, accounting for the intense pain associated with
attachments for the extraocular muscles, and its smooth external surface scleral inflammation (Watson and Young 2004).
rotates easily on the adjacent tissues of the orbit when these muscles Scleral development is under active regulation to ensure an eye of
contract (Ch. 41). The opacity of the sclera helps ensure that only light the correct axial length to produce a focused image (Wallman and
that enters the eye through the pupil reaches the retina. The cornea, Winawer 2004).
on the other hand, not only admits light but also its covering tear film
is the major refractive surface of the eye.
Filtration angle and aqueous drainage
SCLERA Aqueous humour is produced by the ciliary epithelium; it passes
through the pupil and circulates within the anterior chamber, supplying
The sclera accounts for approximately 93% of the outer coat of the eye. the avascular cornea and lens with nutrients and removing metabolic
Anteriorly, it is continuous with the cornea at the corneoscleral junction waste products. It drains from the eye mainly through the trabecular
(see Fig. 42.1). It is punctured by a number of foramina containing meshwork into the canal of Schlemm at the iridocorneal (filtration)
nerves and blood vessels, most notably the optic foramen, which lies angle (see Figs 42.2–42.3), formed between the posterior aspect of the
3 mm medial to the midline and 1 mm below the horizontal, and corneoscleral limbus and the periphery of the iris. Differences in drain-
houses the optic nerve. Smaller openings contain anterior ciliary arteries age angle morphology most probably underlie ethnic variations in the
that penetrate anteriorly, vortex veins that cross the sclera equatorially, prevalence of primary angle closure glaucoma (Wang et al 2012).
and the long and short ciliary nerves and arteries that enter posteriorly. The trabecular meshwork is continuous anteriorly with Descemet’s
There is considerable individual variation in scleral dimensions. The membrane and the endothelium of the cornea. Aqueous humour filters
sclera is thickest at the posterior pole (approximately 1 mm) and from the anterior chamber through interconnected spaces among loose


decreases anteriorly, reaching a minimum equatorially at about half this trabecular fibres, most of which are attached to the anterior, external
thickness. It also thins approaching the optic nerve. The sclera is thinner aspect of the scleral spur. Of the remainder, most are continuous with
when the eye is elongated in myopia. longitudinal fibres of the ciliary muscle, some of which attach to the
Extraocular Longitudinal Oblique ciliary Circular Canal of Fig. 42.2 A meridional section through the anterior
muscle Sclera ciliary muscle muscle ciliary muscle Schlemm Cornea eye, highlighting the ciliary body and drainage
apparatus.
Ciliary body, pars Ciliary body, Ciliary body, pars Scleral Trabecular
plana stroma plicata spur meshwork Iris


EYE
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Limbus
Corneal stroma
Iris
Line or ring of
Conjunctival epithelium
Schwalbe Cornea
Anterior chamber
Conjunctiva
Trabecular Anterior surface of lens
meshwork
Canal of Schlemm Iris process
Scleral spur Iris
Filtration angle
Sclera
Major iridic circle
Ciliary muscle Posterior chamber
B
A
Fig. 42.3 A, A schematic representation of the tissues bordering the anterior chamber angle. The trabecular meshwork is an anulus of tissue spanning
the angle; its meshes are shown in transverse section opposite the canal of Schlemm and partly attached to the scleral spur. A single iris process
bridges the angle, connecting the trabecular meshwork to the anterior tissues of the iris. B, An optical coherence tomography (OCT) in vivo image of the
anterior segment of a 60-year-old Caucasian female taken in dim room light. (B, Courtesy of Mr Gus Gazzard, Consultant Ophthalmic Surgeon,
Moorfields Eye Hospital, London.)
Aqueous Collector Conjunctival Fig. 42.4 Tissues of the
vein channels vessels filtration angle in section. The
approximate borders of the
limbal region are indicated by
the solid lines. Aqueous humour
Cornea drains from the anterior chamber
Episcleral vein at T through the trabecular
Sclera meshwork into the canal of
Schlemm; from here, it flows
Canal of Schlemm through collector channels, either
Intrascleral Schwalbe’s line to the intrascleral venous plexus,
venous plexus where it mixes with blood from
the ciliary venous plexus, or
Scleral spur
directly to the surface tissues of
T
Ciliary venous plexus the eye as an aqueous vein. The
Iris aqueous vein is shown joining an
Ciliary muscle
episcleral vein at the surface to
form a laminated vessel.
Iridocorneal angle Aqueous and blood drain
posteriorly in episcleral veins,
which, in turn, join anterior ciliary
veins.


posterior internal aspect of the scleral spur. The trabecular meshwork to as much as much as 54% (Alm and Nilsson 2009), and decrease with
provides sufficient resistance to aqueous humour outflow to generate age. Since there is no epithelial barrier between the anterior chamber
an intraocular pressure of approximately 15 mmHg. It also acts as a and the ciliary body, aqueous humour is able to enter the loose con-
filter and has the capacity to phagocytose particulate matter, although nective tissue in front of the ciliary muscle and pass between the muscle
overloading may contribute to the pathogenesis of various forms of fibres into the supraciliary and suprachoroidal spaces, where, poten-
obstructive secondary glaucoma (p. 697). tially, it can be absorbed by vessels that drain the uvea. Clinically,
The canal of Schlemm (sinus venosus sclerae) is an anular endothe- aqueous outflow via this route can be increased by topical prostaglan-
lial canal located near the internal surface of the sclera close to the din analogues, which are first-line therapy for the treatment of open
limbus. In section, the canal appears as an oval cleft, with an outer wall angle glaucoma.
that grooves the sclera. Posteriorly, the cleft extends as far as a rim of
scleral tissue, the scleral spur, which, in section, forms a triangle with
its apex directed forwards (see Figs 42.2–42.3A). The canal of Schlemm CORNEA
may be double or multiple in part of its course, and its walls are con-
structed of a continuous single thin endothelial layer. Passage of The avascular cornea is the anterior transparent part of the outer coat.
aqueous humour to the canal probably occurs via giant pinocytotic Convex anteriorly, it projects from the sclera as a dome-shaped eleva-
vacuoles and associated transcellular pores, which form on the inner tion with an area of 1.1 cm2, forming approximately 7% of the external
face of the endothelium and discharge into the canal at the outer face. tunic area. Since it is more curved (average radius, r = 7.8 mm) than the


Aqueous humour passes through a plexus of fine intrascleral vessels that sclera (r = 11.5 mm), a slight sulcus sclerae marks the corneoscleral junc-
connect the canal of Schlemm with episcleral veins (Fig. 42.4). Nor- tion (limbus). The high corneal curvature of the neonate cornea
mally, the canal does not contain blood; pressure gradients prevent the decreases to reach adult levels within a relatively short space of time
reflux of blood, even though the channels between the canal and veins (Friling et al 2004).
have no valves. However, in venous congestion, blood may enter the The cornea is approximately 670 µm thick close to the corneoscleral
canal; the continuous endothelial outer wall of the canal prevents junction, and 520 µm at its centre. At the nasal and temporal limbus,
further reflux. the transition from cornea to sclera occurs in a line that is approxi-
An alternative route for aqueous outflow, the uveoscleral pathway, mately perpendicular to the cornea; this transition occurs more
has been described (Fautsch and Johnson 2006, Goel et al 2010). Esti- obliquely superiorly and inferiorly, with the sclera overlapping the
mates of aqueous drained by this route in humans vary from under 5% cornea to a greater extent anteriorly. Consequently, when viewed from


Outer coat
689
24
RETPAHC
Fig. 42.5 A, A low-power light micrograph of the
five layers of the cornea. B, A high-power light
micrograph of the corneal epithelium and
Bowman’s layer. C, A high-power light
micrograph of the corneal endothelium,
Descemet’s layer and part of the stroma. The
Epithelium darkly staining cells in the stroma are keratocytes.
Bowman’s layer
B
Stroma
Descemet’s layer
A C Endothelium
in front, the corneal perimeter is slightly elliptical, as its horizontal Fig. 42.6 An electron
diameter (11.7 mm) is a little greater than its vertical (10.6 mm). Its micrograph of the
posterior perimeter is circular (diameter 11.7 mm). stroma of the human
Since the cornea carries most of the optical power of the eye, changes cornea, showing the
to its shape can have a significant impact on the refractive state of the geometric precision
eye (p. 699). This has been used to advantage in a number of techniques of the alternation in
for correcting refractive error such as laser refractive surgery. direction of adjacent
layers of fibres.
Microscopically, the cornea consists of five layers: corneal epithe-
(Courtesy of John
lium, anterior limiting lamina (Bowman’s layer), substantia propria
Marshall, St Thomas’
(stroma), posterior limiting lamina (Descemet’s membrane) and
Hospital, London.)
endothelium, arranged anteroposteriorly (Fig. 42.5).
Corneal epithelium
The corneal epithelium accounts for approximately 10% of the corneal
thickness (50 µm). It usually consists of 5–6 layers of cells (Fig. 42.5B)
that protect the ocular surface from mechanical abrasion, form a perme-
ability barrier (to small molecules, water and ions) and prevent the
entry of pathogens. The deepest cells are columnar with flat bases,
rounded apices and large round or oval nuclei. Outside these are 2–3
layers of polyhedral (often wing-shaped) cells. In the more superficial
layers, the cells become progressively flatter and present a smooth, opti-


cally perfect surface. Scanning electron microscopy of surface cells
reveals extensive finger-like and ridge-like projections (microvilli and
microplicae). A complex network of tight junctions links the superficial
cells, consistent with their barrier function.
Anterior limiting lamina (Bowman’s layer)
are the principal factors that determine stromal transparency. Light
scattered by the collagen fibrils is eliminated by destructive interference
The anterior limiting lamina lies behind the corneal epithelium. It
in all directions other than forwards.
contains a dense mass of collagen fibrils set in a matrix similar to
that of the substantia propria. The lamina is 12 µm thick, is readily
Posterior limiting lamina (Descemet’s layer)
distinguishable from the substantia propria because it does not
contain fibroblasts, and appears amorphous by light microscopy
(see Fig. 42.5B). The posterior limiting lamina covers the substantia propria posteriorly.
It is thin and apparently homogeneous, and is regarded as the basement
Substantia propria (stroma) membrane of the endothelium (see Fig. 42.5C). Some 4 µm thick at
birth, it may increase to 12 µm by the eighth decade.
The substantia propria is approximately 500 µm thick and forms the
Endothelium
bulk of the cornea. It is a compact and transparent layer, composed of
200–250 sequential lamellae, each made up of fine parallel collagen
fibrils mainly of type I collagen. Flat dendritic interconnecting fibro- The endothelium covers the posterior surface of the cornea and consists
blasts (keratocytes) form a coarse mesh between the lamellae. Alternate of a single layer of squamous cells (see Fig. 42.5C) with prominent
lamellae are typically orientated at large angles to each other (Fig. interdigitations between adjacent cells, which are also connected by
42.6). X-ray diffraction studies indicate that they run along two pre- tight and gap junctions. When viewed en face, the endothelium appears
ferred directions – superior–inferior and nasal–temporal – to account as a mosaic of polygonal (typically hexagonal) cells. As these cells have


for the additional tensile stress exerted by the recti along these merid- a limited capacity for mitosis, in response to pathology, trauma, age
ians (Boote et al 2005). Each lamella is approximately 2 µm thick and and prolonged contact lens wear, the endothelial mosaic becomes less
of variable width (10–250 µm or, rarely, more). In the central cornea, regular, and shows a greater variation in cell size (pleomorphism) and
fibrils within the lamellae have a similar diameter of approximately shape (polymegathism), as cells spread to fill gaps caused by cell loss.
31 nm. This increases slightly with age and approaching the limbus. The numerous mitochondria and prominent rough endoplasmic reticu-
The small size of the fibrils (much smaller than the wavelength of light), lum within these cells reflects their high metabolic activity. Thus, for
along with the regularity of their spacing (maintained by collagen– example, active pumping mechanisms largely control the degree of
proteoglycan interactions) and the careful control of corneal hydration, corneal hydration.


EYE
690
4
NOITCES
Fig. 42.7 Drawing of a
Pigment epithelium histological section through the
of retina
choroid close to the posterior
Lamina vitrea (Bruch’s membrane) pole.
Choriocapillaris
Arteriole Small vessel layer
Venule
Large vessel layer
Suprachoroid
Inner part of sclera
Corneal innervation et al 2012) and is greatest behind the macula. These dimensions are
influenced by several factors, including age (Park and Oh 2013), axial
length, central corneal thickness and time of day, and vary in pathologi-
The cornea is innervated by numerous branches of the ophthalmic
cal conditions such as angle closure.
nerve, which either form an anular plexus around the periphery of the
The choroid is pierced by the optic nerve where it is firmly adherent
cornea, or pass directly from the sclera and enter the corneal stroma
to the sclera. Elsewhere, its external surface is only loosely connected
radially as 70–80 small groups of fibres. On entering the cornea, the
to the sclera by the suprachoroid layer (lamina fusca). Internally, it is
few myelinated nerves lose their myelin sheaths and ramify throughout
attached to the retinal pigment epithelium, and at the optic disc is
the anterior corneal stroma in a delicate reticulum, their terminal fila-
continuous with the pia-arachnoid tissues around the optic nerve.
ments forming an intricate subepithelial plexus. Axon bundles from this
Four layers can be identified in transverse section (Fig. 42.7; see also
plexus cross the anterior limiting membrane and form a sub-basal
Fig. 42.22): suprachoroid, vascular stroma, choriocapillaris and lamina
plexus from which individual beaded axons pass to more superficial
vitrea (Bruch’s membrane).
epithelial layers, eventually terminating as free nerve endings. Corneal
nerves provide the afferent arm of the blink and lacrimation reflexes
Suprachoroid
(Ch. 41) and may also have a neurotrophic function (Müller et al 2003).


The suprachoroid covers the external surface of the choroid; it is approx-
CORNEOSCLERAL JUNCTION (LIMBUS)
imately 30 µm thick and composed of delicate non-vascular lamellae,
each one a network of fine collagen and elastic fibres, fibroblasts and
The limbus marks the transitional zone between the cornea and sclera melanocytes. Ciliary nerves and long posterior ciliary arteries pass for-
(see Fig. 42.3B). Here, the corneal epithelium merges with the epithe- wards to the anterior uvea in this layer.
lium of the conjunctiva, which thickens (up to 12 cells). Bowman’s
layer terminates and the corneal stromal collagen loses its regularity. As Vessel layer (stroma)
the cornea contains neither blood nor lymphatic vessels, the capillaries
of the conjunctiva and episclera end in loops near the limbus. Inter-
Internal to the suprachoroid lies a layer composed mainly of arteries
nally, Descemet’s membrane disperses into the fibres of trabecular
and veins, but also some loose connective tissue containing scattered
meshwork and the corneal endothelium is continuous with that cover-
pigment cells. These melanocytes limit the passage of light through the
ing the trabeculae. The limbus forms a convenient surface landmark for
sclera to the retina. More importantly, like the retinal pigment epithe-
ocular surgery and intravitreal injection. A position 4 mm posterior to
lium, they also absorb light traversing the retina that is not absorbed
the limbus, for example, indicates the pars plana of the ciliary body
by the photoreceptors, so preventing internal reflection.
(orbiculus ciliaris) in adults, through which safe surgical access to the
The blood supply of the choroid, as well as the rest of the uvea, is
posterior segment of the eye can be achieved.
summarized in Figure 42.8. Short posterior ciliary arteries enter the eye
The corneal epithelium does not possess stem cells and its replace-
through the sclera near the optic disc and supply the posterior choroid.
ment depends on the centripetal migration of cells from the edges of
These vessels branch and gradually decrease in size as they approach


the cornea. These cells are the progeny of mitotic limbal stem cells
the retinal border. The choroidal stroma can be divided into layers
located within radially orientated epithelial ingrowths (palisades of
based on the change in the calibre of these vessels: an outer layer of
Vogt).
larger vessels (Haller’s layer) and an inner layer of smaller vessels (Sat-
tler’s layer), which eventually give rise to the choriocapillaris (see Fig.
UVEA 42.7). Long posterior ciliary arteries and recurrent branches of anterior
ciliary arteries supply the anterior part of the choriocapillaris.
Veins within the choroid converge spirally on to four, or very occa-
The vascular tunic of the eye consists of the choroid, ciliary body and
sionally more, principal vortex veins. These pierce the sclera behind the
iris, which collectively form a continuous structure: the uvea (see Fig.
equator to reach tributaries of the ophthalmic veins.
42.1). The choroid covers the internal scleral surface and extends for-
The vessels of the choroid have a rich autonomic vasomotor supply.
wards to the ora serrata. The ciliary body continues forwards from the
The blood flow through the choroid is high, a feature probably
choroid to the circumference of the iris, which is a circular diaphragm
associated with an intraocular pressure of 15–20 mmHg, which means
behind the cornea and in front of the lens, forming an almost central
that a venous pressure above 20 mmHg is required to maintain circula-
aperture, the pupil.
tion. The choroidal perfusion rate exceeds that required to supply nutri-
ents and may serve to cool the retina during exposure to bright light.
CHOROID
Choriocapillaris
The choroid is a thin, highly vascular, pigmented layer that lines almost
five-sixths of the eye posteriorly. Its mean thickness, measured by The choriocapillaris provides nutrients to the avascular outer five layers
optical coherence tomography (OCT), is approximately 230 µm (Arora of the retina and is composed of large (up to 20 µm thick), densely


Uvea
691
24
RETPAHC
D
J
e k
o l
n
f
g
n
e
D
C
A h
b m
i
b
f
C
e D
C
J
D
Fig. 42.8 The vasculature of the uveal tract. The long posterior ciliary arteries, one of which is visible (A), branch at the ora serrata (b) and feed the
capillaries of the anterior part of the choroid. Short posterior ciliary arteries (C) divide rapidly to form the posterior part of the choriocapillaris. Anterior
ciliary arteries (D) send recurrent branches to the choriocapillaris (e) and anterior rami to the major arterial circle (f). Branches from the circle extend into
the iris (g) and to the limbus. Branches of the short posterior ciliary arteries (C) form an anastomotic circle (of Zinn) (h) round the optic disc, and twigs
from this (i) join an arterial network on the optic nerve. The vortex veins (J) are formed by the junctions (k) of suprachoroidal tributaries (l). Smaller
tributaries are also shown (m, n). The veins draining the scleral venous sinus (o) join anterior ciliary veins and vorticose tributaries. (With permission from
Hogan MJ, Alvarado JA, Weddell JE 1971 Histology of the Human Eye. Philadelphia: WB Saunders.)
packed, freely anastomosing, fenestrated capillaries. While pericytes Externally, the ciliary body may be represented by a line that extends
occur mainly on the scleral surface, most fenestrations face the retina. from approximately 1.5 mm posterior to the limbus of the cornea (cor-
The permeability of choriocapillaris is exceptionally high, even com- responding also to the scleral spur) to a line 7.5–8 mm posterior to this
pared to other structures invested with fenestrated capillaries. on the temporal side, and 6.5–7 mm on the nasal side. The ciliary body
is thus slightly eccentric. It projects posteriorly from the scleral spur,


Lamina vitrea (Bruch’s membrane) which is its attachment, with a meridional width varying from 5.5 to
6.5 mm. Internally, it exhibits a posteriorly crenated or scalloped
periphery, the ora serrata, where it is continuous with the choroid and
The lamina vitrea lies between the choriocapillaris and the retinal
retina (Figs 42.9–42.10). Anteriorly, it is confluent with the periphery
pigment epithelium, from both of which it is derived. Under the light
of the iris, and externally, it bounds the iridocorneal angle of the ante-
microscope, it appears as a homogeneous layer, 2–4 µm in diameter
rior chamber.
and consists largely of a central elastic fibre mesh, although some
In cross-section, the ciliary body is composed of four layers (from
authors include flanking internal and external layers of collagen and
internal to external): a double layer of epithelial cells, the stroma, ciliary
the basal laminae of the choriocapillaris and retinal pigment epithe-
muscle and a supraciliary layer (see Fig. 42.2).
lium in this structure. Its function is thought to be related to the passage
Meridionally, the ciliary body can be divided into two parts (see Figs
of fluid and solutes from the choroidal capillaries to the retina. In
42.2, 42.10). Anteriorly, the ridged pars plicata (corona ciliaris) sur-
advancing years, extracellular deposits may accumulate in this mem-
rounds the base of the iris and accounts for about one-third of the
brane (drüsen), which impairs the exchange of gases, nutrients and
ciliary body. Posteriorly, the relatively smooth and thin pars plana
metabolites between the choroidal blood and the outer layers of the
(orbiculus ciliaris) lies adjacent to the ora serrata, and forms a conven-
retina, potentially contributing to degenerative disease in the photo-
ient access point for instruments during vitreoretinal surgery and for
receptor layer of the neural retina.
intraocular injection. The whole ciliary body is covered by a double


epithelium, in which the inner layer is unpigmented, while the outer
layer contains melanin. At the ora serrata, the retinal pigment epithe-
CILIARY BODY lium is continuous with the outer pigmented epithelium of the pars
plana, while the neural retina is replaced by inner unpigmented ciliary
The ciliary body serves to anchor the lens via suspensory ligaments, and epithelium (see Fig. 42.24). Anteriorly, this double epithelium contin-
by the contraction of its smooth muscle changes the refractive power ues over the pars plicata until it merges with the double epithelium on
of the lens (accommodation). Its anterior internal surface is also the the posterior surface of the iris (where the inner layer of cells also
source of aqueous humour, while posteriorly its inner surface is con- accumulates melanin). The anterior pars plicata is ridged meridionally
tiguous with the vitreous humour and secretes several of its compo- by 70–80 ciliary processes radiating from the base of the iris (see Figs
nents. The anterior ciliary arteries and the long posterior ciliary arteries 42.9–42.10). In the young eye, these process are approximately parallel-
meet in the ciliary body, and the major nerves to all the anterior tissues sided structures, but in the adult, their flanks become less regular and
of the eyeball pass through it. appear thicker. A minor ridge, or ciliary plica, lies in the valley between


EYE
692
4
NOITCES
Fig. 42.9 The ciliary region seen from the ocular
interior. Above is the periphery of the lens,
i
attached by the fibres of the zonule (suspensory
ligament) to the processes of the pars plicata
h (corona ciliaris) of the ciliary body (a). The pars
plana ciliaris (orbiculus ciliaris) (b) has a scalloped
boundary, the ora serrata (c), which separates it
from the retina (d). Flanking the ‘dentate bays’ (e)
of the ora serrata are the dentate processes (f),
with which linear ridges or striae (g) are
continuous; the striae extend forwards between
the main ciliary processes, providing an
attachment for the longer zonular fibres. The
posterior aspect of the iris shows radial (h) and
circumferential (i) sulci. (With permission from
Hogan MJ, Alvarado JA, Weddell JE 1971
Histology of the Human Eye. Philadelphia: WB
Saunders.)
a
g
f
e
b
e
d
c
Dentate process Dentate bay Ora serrata most of the processes. The crests of the processes are less pigmented,
giving them the appearance of white (or light) striae, from which the
name ciliary is derived. The suspensory ligaments attached to the lens
extend into the valleys between the ciliary processes and pass beyond
them to fuse with the basal lamina of the superficial epithelial layer of
pars plana. Their sites of attachment are marked by striae that pass back
from the valleys of the pars plicata, across the pars plana, almost as far
as the apices of the dentate processes of the ora serrata (see Fig. 42.9).
Ciliary epithelium
The ciliary epithelium is bilaminar, consisting of two layers of epithelial
cells that are derived embryonically from the two layers of the optic
cup. The superficial layer consists of columnar cells over the pars plana,
and cuboidal cells over the ciliary processes of the pars plicata; it
becomes irregular and more flattened between the processes. These cells


contain little or no pigment. The outer layer of the ciliary epithelium,
in contrast, contains cuboidal cells that are loaded with melanin. Nor-
mally, the two layers are firmly united but fluid may separate them
pathologically. The pigment layer is attached to the stroma of the ciliary
Pars plana of Ciliary processes of Iris Lens
body by its basal lamina, which continues back into the basal lamina
ciliary body pars plicata
of the choroid. As a consequence of the invagination of the optic cup
Fig. 42.10 The posterior aspect of the anterior half of the eye, showing
during development, a basal lamina covers the free surface of the
the termination of the neural retina at the ora serrata and the ciliary body.
bilayer, which is continuous with the internal limiting membrane of
The lens has retained sufficient transparency to reveal the iris border; the
the retina.
crenated perimeter of the lens is due to tension imposed by the attached
The ciliary epithelium is responsible for the secretion of aque-
suspensory ligaments (unseen).
ous humour, while the outer pigmented epithelium additionally


Uvea
693
24
RETPAHC
Fig. 42.11 The ciliary muscle and its components.
The meridional or longitudinal (1), radial or oblique
(2), and circular or sphincteric (3) layers of muscle
a fibres are displayed by successive removal
towards the ocular interior. The cornea and sclera
have been removed, leaving the canal of Schlemm
c (a), collecting venules (b), scleral spur (c) and
trabecular meshwork (d). The meridional fibres (1)
often display acutely angled junctions (d) and
terminate in epichoroidal stars (e). The radial fibres
meet at obtuse angles (f) and similar junctions, at
b even wider angles (g), occur in the circular ciliary
muscle. (With permission from Hogan MJ,
Alvarado JA, Weddell JE 1971 Histology of the
d Human Eye. Philadelphia: WB Saunders.)
g a
3
c b
d
f
1
3
2
d
2
e
e
1
contributes to the eye’s ‘black box effect’, like the retinal pigment Accommodation reflex
epithelium, choroidal pigment and posterior iris epithelium, absorb-
At rest, distant objects are focused on the retina in an emmetropic eye.
ing stray light to enhance image quality.
In order to focus closer objects, the dioptric power of the eye has to be
increased, which is achieved by increasing the curvature of the lens. At
Ciliary stroma
rest, the lens is under tension from the zonular ligaments and hence
flattened. On accommodation, the ciliary muscle contracts, moving the
The ciliary stroma is composed largely of loose bundles of collagen, ciliary body forwards and inwards towards the optic axis. All parts of
which form a considerable mass between the ciliary muscle and over- the muscle act in concert and tension on the zonular ligaments is
lying processes, and extend into both of them. It also contains numer- relaxed. As the lens is covered by an elastic capsule, once tension on it
ous larger branches of the ciliary vessels. A dense reticulum of large is released, it assumes a more convex shape suitable for focusing closer


(up to 35 µm in diameter) fenestrated capillaries is concentrated in the objects. The radius of curvature of the anterior lens surface changes
ciliary processes, facilitating the passage of substances from the blood most during accommodation. This classic view of accommodation, first
plasma during aqueous production. Anteriorly, near the periphery of proposed in principal by Helmholtz nearly 100 years ago, remains
the iris, the major arterial circle (see Fig. 42.8) is formed by anastomo- generally accepted, although details of the roles of various ocular struc-
sis between the anterior ciliary arteries and long posterior ciliary arter- tures continue to be debated (Charman 2008).
ies, branches of the ophthalmic artery (see Fig. 41.13). Ciliary veins, Information from the retina passing to the visual cortex does not
also draining the iris, pass posteriorly to join the vortex veins of the constitute the afferent limb of a simple reflex in the usual sense of the
choroid. term, but permits the visual areas to assess the clarity of objects in the
visual field. Cortical efferent information passes to the pretectal area
Ciliary muscle
and thence to the Edinger–Westphal nucleus, which contains pregan-
glionic parasympathetic neurones whose axons travel in the oculo-
Ciliary muscle is composed of smooth muscle cells, most of which are motor nerve and synapse in the ciliary ganglion within the orbit (Fig.
attached to the scleral spur and arranged in three different orientations. 42.12). Postganglionic fibres (short ciliary nerves) innervate the ciliary
The outermost fibres are meridional or longitudinal, and pass posteri- muscle, causing it to contract. There is also a sparse sympathetic inner-
orly into the stroma of the choroid. The innermost fibres swerve acutely vation of ciliary muscle, which has a very limited capacity to relax the
from the spur to run circumferentially as a sphincter near the periphery muscle.
of the lens. Obliquely interconnecting radial fibres run between these Accommodation is usually accompanied by constriction of the pupil
two muscular strata, frequently forming an interweaving lattice (see brought about by contraction of the sphincter pupillae, and convergent


Fig. 42.2; Fig. 42.11). eye movements caused by contraction of the medial, superior and


EYE
694
4
NOITCES
Sphincter pupillae Iris Fig. 42.12 The neural pathways of the pupillary light
reflex (left) and the accommodation reflex (right). (From
Medial
Ciliary muscle Oxford Textbook of Functional Anatomy, Vol 3 Head
rectus
and Neck, MacKinnon P, Morris J (eds) 1990. With
permission of Oxford University Press.)
Optic nerve Short ciliary
nerves
Ciliary ganglion
Ciliary ganglion
Optic tract
Oculomotor
nerve Fibres in
internal capsule
Edinger–Westphal
preganglionic Lateral
nucleus geniculate
nucleus
Pretectal nucleus
To sympathetic centre
Superior
in spinal cord for control
longitudinal
of dilator pupillae
fasciculus
Optic radiation
Visual cortex
inferior recti (all innervated by the oculomotor nerve). This is the ‘near border layer blends with the trabecular connective tissue of the irido-
triad’ that may become disrupted in various diseases. corneal angle; at the pupillary rim, it meets the epithelium of the
posterior surface of the iris.
Supraciliary layer The colour of the iris is a product of the combined effect of reflection/
absorption by the iridial connective tissue and the concentration of
pigment in the anterior border layer and, to a lesser extent, in the iris
The thin supraciliary layer separates the sclera from the ciliary muscle
stroma. The distribution of pigment is often irregular, which produces
and is largely composed of collagen fibres derived from the two layers
a flecked appearance. When pigment is largely absent, other than in the
it divides. It also forms an alternative ‘unconventional’ route (other
posterior epithelial layers (the condition at birth), the colour is light
than the canal of Schlemm) for the drainage of aqueous humour.
blue.
IRIS Stroma
The iris is an adjustable diaphragm around a central aperture (slightly The stroma of the iris is formed of fibroblasts, melanocytes and a loose
medial to true centre), the pupil. It lies between the cornea and lens, collagenous matrix but no elastic tissue. The intercellular spaces appear


and is immersed in aqueous fluid (see Fig. 42.1), partially dividing the to communicate freely with the anterior chamber. A few large, heavily
anterior segment into an anterior chamber, enclosed by the cornea and pigmented ‘clump cells’ may be present; these are phagocytes and
iris, and a posterior chamber, situated between the iris and the lens contain lysosomes and ingested melanosomes. The stroma contains
anterior to the vitreous. The efficacy of the iris as a light stop is mainly regional vessels and nerves. An aggregation of smooth muscle cells near
due to a densely pigmented posterior double epithelium. The pupillary the pupillary rim forms an anular contractile sphincter pupillae (see
aperture is adjusted by the action of two muscles, dilator and sphincter below).
pupillae.
Seen from the front, the iris is divided into a large ciliary zone adja- Epithelial layers
cent to the ciliary body and a smaller, inner, pupillary zone (Fig. 42.13).
The two regions join at the collarette. The anterior surface of the iris
The epithelial surface covering the iris posteriorly is a continuation of
often contains large depressions (crypts of Fuchs), and at the pupillary
the bilaminar epithelium of the ciliary body and is formed from the
margin, the posterior pigmented epithelium is visible as the pupillary
two layers of the optic cup. The pupil, through which this epithelium
ruff.
curves for a short distance on to the anterior surface as the pigment ruff,
In transverse section, several subdivisions of the iris are evident (Fig.
corresponds to the opening of the optic cup.
42.14). From anterior to posterior, they are an anterior border layer, the
The layer of epithelial cells nearest the stroma is, somewhat confus-
stroma (which contains the sphincter pupillae), and two pigmented
ingly, termed the anterior epithelium, although it lies posterior to the
epithelial layers, the most anterior of which contains the dilator pupil-
stroma. Its cells are pigmented, as are those of the corresponding layer
lae. It is thinnest at its root (approximately 200 µm), where the ciliary


in the ciliary epithelium. They give rise to the dilator pupillae (see
body is attached, and thickest at the collarette.
below). Vitreal to this stratum is a layer of heavily pigmented cells, the
posterior epithelium, which is continuous with the inner non-
Anterior border layer
pigmented layer of the ciliary epithelium. As is readily apparent from
in vivo scans, the pupillary region of the iris rests on the front surface
The anterior surface of the iris is not a distinct epithelium but a modi- of the lens (see Fig. 42.3B). Its posterior surface therefore bears numer-
fied layer of the iris stroma, formed mainly by an increased number of ous radial ridges that facilitate the movement of aqueous humour from
fibroblasts that constitute a network on the anterior surface with a layer the posterior to the anterior chamber. Adjacent epithelial cells are
of underlying melanocytes. At the periphery of the iris, the anterior extensively joined by various junctions that ensure the layer can


Uvea
695
24
RETPAHC
Brown
iris
F anig i.
r
i4 s2
.
. T1 h4
e
A
p
om se teri rd ioio
r
n sa ul
r
fs ae cc et io isn lio nf
e d
CM with a double epithelium (E, E′); the
c arrow points to the processes of
I the anterior layer of the epithelium
forming the dilator pupillae muscle.
B The iris is in a contracted state, as
RT
CP shown by the thickened epithelium
opposite the dilator muscle and
Blue
iris
t bh yin tn hi en g
s
ho op rp tno es sit se oth
f
e
th
s ep ph uin pc ilt le ar r,
y
and
zone. Abbreviations: A, anterior
c PF border layer; C, collarette; CM,
ciliary muscle; CP, ciliary
processes; I, major iridic circle; P,
A
pupillary region of the iris; PF, folds
in anterior surface towards the root;
R, pupillary ruff; RT, root; S,
sphincter pupillae muscle; ST,
d e stroma.
A
f
V
e
ess
sl E´
g
E
e
ST
h
i
g
e h
Posterior
surfac
j
Muscles
S
C
P
k R
Dilator pupillae
The dilator (dilatator) pupillae forms a thin layer that lies immediately
anterior to the epithelium of the posterior surface of the iris. Its ‘fibres’
Fig. 42.13 A composite view of the surfaces and internal strata of the iris. are the muscular processes of the anterior layer of this epithelium,
In a clockwise direction from above, the pupillary (A) and ciliary (B) zones whose cells are therefore myoepithelial. Myofilaments are present
are shown in successive segments. The first (brown iris) shows the throughout these cells but are more abundant in their fusiform basal
anterior border layer and the openings of crypts (c). In the second


muscular processes, which are approximately 4 µm thick, 7 µm wide
segment (blue iris), the layer is much less prominent and the trabeculae of
and 60 µm in length. They form a layer 3–5 elements thick through
the stroma are more visible. The third segment shows the iridial vessels,
most of the iris, from its periphery to the outer perimeter of the sphinc-
including the major arterial circle (e) and the incomplete minor arterial
ter, which it slightly overlaps. Here the dilator thins out and sends spurs
circle (f). The fourth segment shows the muscle stratum, including the
to blend with the sphincter. Unlike the apical parts of the myoepithelial
sphincter (g) and dilator (h) of the pupil. The everted ‘pupillary ruff’ of the
cells, these have a basal lamina and are joined by gap junctions like
epithelium on the posterior aspect of the iris (d) appears in all segments.
The final segment, folded over for pictorial purposes, depicts this aspect those between the sphincteric muscle cells. Small, unmyelinated axons
of the iris, showing radial folds (i and j) and the adjoining ciliary processes pass between, and terminate on, their muscular processes (see Fig.
(k). (With permission from Hogan MJ, Alvarado JA, Weddell JE 1971 42.15).
Histology of the Human Eye. Philadelphia: WB Saunders.)
Innervation of muscles of the iris
The iris is innervated mainly by the long and short ciliary nerves. Short
withstand the excursions of the iris during changes in pupillary size ciliary nerves, which contain parasympathetic, postganglionic, myelin-
(Fig. 42.15). ated axons derived from the ciliary ganglion (see Figs 41.17, 42.12),
innervate the sphincter pupillae, losing their myelin well before
entering the muscle. The dilator is supplied with sympathetic, non-
Iris muscles
myelinated, postganglionic fibres from the superior cervical ganglion;
their routes are less well established. Some go via the ciliary ganglion
Sphincter pupillae


and reach the eye in the short ciliary nerves, whereas other fibres may
The sphincter pupillae is a flat anulus of smooth muscle approximately travel in the long ciliary nerves, which are branches of the nasociliary
750 µm wide and 150 µm thick. Its densely packed, fusiform muscle nerve. An additional small fraction of nerve endings in the dilator and
cells are often arranged in small bundles, as in the ciliary muscle, and sphincter muscles have been identified as parasympathetic and sympa-
pass circumferentially around the pupil (see Fig. 42.13). Collagenous thetic, respectively, in experimental animal studies, including those on
connective tissue lies in front of and behind the muscle fibres. It is very primates. Although ganglion cells have been noted in the iris, the
dense posteriorly, where it binds the sphincter to the pupillary end of majority of axons are probably postganglionic. They form a plexus
the dilator muscle, and is attached to the epithelial layer at the pupil around the periphery of the iris, from which fibres extend to innervate
margin. Small axons, mostly non-myelinated, ramify in the connective the two muscles, the vessels and the anterior border layer; some fibres
tissue between bundles. may be afferent and others are vasomotor.


EYE
696
4
NOITCES
Stromal Nerve fibre Zonula Gap Stromal
collagen bundle adherens junctions melanocyte
Anterior epithelium
Posterior epithelium
Tight junction
Intercellular process
Desmosome
Circumferential fold
Basal lamina
Fig. 42.15 Posterior structures of the iris. The dilator pupillae is shown in transverse section on the right and in longitudinal section on the left (the arrow
shows a rarer deeper nerve terminal).
Pupillary light reflex around the carotid artery. Some of the axons from the plexus form the
Pupillary diameter varies from around 2 mm when fully constricted sympathetic root of the ciliary ganglion, passing through the ciliary
(miosis) in bright light to at least 8 mm when dilated in darkness ganglion without synapsing; mostly travelling in the short ciliary nerves,
(mydriasis), and has an even wider range under the influence of drugs. they innervate the dilator.
The resulting variation in pupil area (maximally a factor of 16) will
obviously affect the amount of light impinging on the retina. However, Vascular supply of the iris
compared to the total range of illumination within which humans can
maintain some degree of vision (approximately 10 log units), this effect, The iris receives its blood supply from the long posterior and anterior
though important, is small. Most mechanisms for dark/light adaptation ciliary arteries (see Figs 41.13, 42.8). On reaching the attached margin
are retinal, and neural or biochemical in nature. Enhancing visual acuity of the iris, both long ciliary arteries divide into an upper and a lower
by restricting light to the centre of the lens, and thereby decreasing the branch. The branches anastomose with the corresponding contralateral
amount of spherical aberration, is at least as important a function of arteries, and with the anterior ciliary arteries, to form the major arterial
pupillary constriction. (iridic) circle (circulus arteriosus major) at the base of the iris (see Figs
If only one eye is illuminated, the pupil of that eye constricts (direct 42.13–42.14). Vessels converge from this circle towards the free margin


response), as does the pupil of the contralateral, unilluminated, eye of the iris, where they form loops and become veins. At the level of the
(consensual response). While change in pupillary diameter is usually collarette, arteries and veins anastomose to form an incomplete minor
considered a reflex response to changes in light level, the pupil also iridic circle (circulus arteriosus minor). The smaller arteries and veins
constricts on viewing near objects (as part of the near triad; p. 693) and are very similar in their structure and are often slightly helical, which
in response to painful stimuli; it can also be influenced to some degree allows them to adapt to changes in iridial shape as the pupil varies in
by more complex cortical factors. size. All of the vessels, including the capillaries, have a non-fenestrated
In pupillary constriction, light acting on both traditional retinal endothelium and a prominent, often thick, basal lamina. There is no
photoreceptors (rods and cones) and on intrinsically photosensitive elastic lamina in the arteries or veins, and there are few smooth muscle
retinal ganglion cells gives rise to activity in retinal ganglion cells. This cells, especially in the veins. Connective tissue in the tunica media is
activity is conducted along the optic nerve, through the optic chiasma loose, whereas the adventitia is remarkably dense and collagenous, so
and along the optic tract. Although the majority of tract fibres end in that it appears to form almost a separate tube.
the lateral geniculate nucleus of the thalamus, a small number leave the
optic tract before it reaches the thalamus, at the superior brachium, and
LENS AND HUMOURS
synapse in the olivary pretectal nucleus. The information is relayed from
the pretectal nucleus by short neurones that synapse bilaterally on
preganglionic parasympathetic neurones in the Edinger–Westphal The cornea, aqueous humour, lens and vitreous body, often collectively
nucleus (in the oculomotor nerve complex in the rostral midbrain). termed the ocular media, serve to form an image on the retina by trans-


Efferent impulses pass along parasympathetic fibres carried by the ocu- mitting and refracting light. Additionally, the aqueous provides nutri-
lomotor nerve to the orbit, where they synapse in the ciliary ganglion. ents to the avascular cornea and lens, and removes their metabolic
Postganglionic fibres travel in the short ciliary nerves to the sphincter waste, as well as generating the intraocular pressure that maintains the
pupillae, which reduces the size of the pupil when it contracts (see shape of the eye.
Fig. 42.12).
Pupillary dilation is brought about by lessening the parasympathetic
drive to the sphincter (see above) and by sympathetic activation of the AQUEOUS HUMOUR
dilator. Sympathetic preganglionic fibres arise from neurones in the
lateral column of the first and second thoracic segments, and pass via Aqueous humour is derived from the plasma within the fenestrated
the sympathetic trunk to the superior cervical ganglion. Postganglionic capillaries of the ciliary processes. The major component of aqueous,
neurones travel up the neck next to the internal carotid artery as the like plasma, is water and the composition of the two fluids is broadly
internal carotid nerve; at the level of the cavernous sinus, the nerve similar, although they do differ in the concentration of some electro-
breaks up to form an interweaving network of fibres, the carotid plexus, lytes and organic solutes. In the interests of optical clarity, the


Lens and humours
697
24
RETPAHC
Suspensory ligaments
Posterior
chamber
Vitreous
chamber
Anterior
chamber Cortex
Anterior vitreal
membrane
Adult Fig. 42.17 A section through the anterior layers of the lens. The thin
Infantile Parts of capsule covers the single row of epithelial cells (arrow), and the lens
Fetal nucleus substance is composed of regularly stacked younger fibres and more
Embryonic densely stained and complex older deeper fibres.
Nucleus
amount of short-wave radiation transmitted diminishes until, in old
Fig. 42.16 A sagittal section through part of the lens and related age, the lens takes on an amber tinge as it absorbs visible short-wave
structures. The cortex is distinguished from the nucleus, which is radiation, decreasing blue sensitivity in older people. In cataract, the
composed of embryonic, fetal, infantile and adult parts. The capsule is
lens gradually becomes opaque.
drawn in blue, exaggerated in thickness 100 times, and is based on
The dimensions of the lens are optically and clinically important,
observations from a 35-year-old.
but change with age as a consequence of continuous growth. Its equa-
torial diameter at birth is 6.5 mm, increasing rapidly at first, then more
slowly to 9.0 mm at 15 years of age, and even more gradually to reach
blood–aqueous barrier also ensures a very low concentration of protein
9.5 mm in the ninth decade. Its axial dimension increases from
in the aqueous (generally less than 1% of the level in plasma). Inflam-
3.5–4.0 mm at birth to 4.75–5.0 mm at age 95. The lens flattens during
mation of the anterior uvea can lead to a breakdown of this barrier and
the first decade of life (Mutti et al 1998). Average adult radii of the
the presence of protein in the aqueous, resulting in light scatter that is
anterior and posterior surfaces of the lens are 10 mm and 6 mm, respec-
manifest clinically as ‘flare’.
tively. These reduce in later life, the anterior surface increasing most in
The aqueous is actively secreted into the posterior chamber by the


curvature as the lens thickens, so that, in old age, the lens pushes the
epithelium overlying the ciliary processes. It passes around the equator
iris forwards slightly, predisposing the elderly eye to angle closure
of the lens and flows through the pupil into the anterior chamber,
glaucoma.
where it circulates before being drained at the iridocorneal angle. Most
The lens consists of three layers (Fig. 42.17). Its bulk is composed
aqueous is drained from the eye through the trabecular meshwork into
of elongated cells (lens fibres), which anteriorly, as far as the equator,
the canal of Schlemm; from here, it drains into episcleral veins. However,
are covered by a single layer of epithelial cells, and the whole is sur-
some exits through the ciliary muscle into the supraciliary and supra-
rounded by the lens capsule. The lens is avascular and devoid of nerve
choroidal spaces (uveoscleral pathway).
fibres or other structures that might affect its transparency. Its surface
Any interference with the drainage of aqueous into the canal of
forms a very effective barrier against invasion by cells or elements of
Schlemm increases intraocular pressure and leads to glaucoma. Glau-
the immune system, and so creates an immunologically sequestered
coma is either ‘primary’, or secondary to a specific anomaly or disease
environment. It is unique because it retains all the cells formed through-
of the eye. Primary glaucoma can be either ‘closed angle’, where the
out its life.
filtration angle is narrowed by the proximity of the root of the iris to
the cornea, or, more commonly ‘open angle’, where aqueous access to
Lens capsule
angle tissues is unimpeded. In the most common form of primary open
angle glaucoma, pathological changes within the trabecular meshwork
reduce the facility of aqueous drainage, thus raising intraocular pres- The lens capsule is a basement membrane that covers the surface of the
sure. Sustained raised pressure leads to progressive defects in the visual lens. It consists of various classes of collagen fibre (I, III and IV), as well
field, because of either direct mechanical damage to retinal ganglion as a range of glycosaminoglycans and glycoproteins. It is derived from


cell axons (particularly at the optic nerve head), or impairment of the the anterior lens epithelial cells and their fetal precursors, and is firmly
optic nerve head blood supply, or both. attached to the epithelium anteriorly and to lens fibres posteriorly. The
capsule is elastic, a property it owes to the arrangement of its collagen,
and which is central to the process of accommodation. Capsule thick-
LENS ness varies with position and age. One view is that, in adults, it is
thicker at the anterior pole (12–14 µm) and equator than at the pos-
The lens is a transparent, encapsulated, biconvex body bathed in terior pole, with a band of increased thickness between the pole and
aqueous humour, which serves to adjust the focus of the eye. Posteri- equator (anteriorly, 20–24 µm) (see Fig. 42.16). Zonular fibres insert
orly, it contacts the hyaloid fossa of the vitreous body. Anteriorly, it into the capsule at the equator. They are composed of thin (4–7 nm)
forms a ring of contact with the posterior border of the pupillary region fibrils with hollow centres, and resemble fibrils associated with elastic
of the iris but, further away from the axis of the lens, the gap between connective tissue.
the lens and iris increases to form the posterior chamber of the eye (see
Lens epithelium
Fig. 42.1; Fig. 42.16). The lens is encircled by the ciliary processes, and
is attached to them by the zonular fibres, which issue mainly from the
pars plana of the ciliary body. Collectively, the fibres form the zonule, The anterior surface of the lens between the outer capsule and the
which holds the lens in place and transmits the forces that stretch the underlying lens fibres is covered by a layer of simple, roughly cuboidal
lens. (10 µm high and 13 µm wide), epithelial cells that, in surface view, are
The anterior convexity of the lens is less steep than that of the pos- polygonal (see Fig. 42.17). These cells differentiate into lens fibres; they
terior surface. The central points of these surfaces are the anterior and undergo mitosis at a germinative zone just anterior to the equator and


posterior poles of the lens and a line connecting them is its axis. The are displaced towards the equator, where they synthesize characteristic
marginal circumference of the lens is its equator. lens fibre proteins and undergo extreme elongation. As other cells
At birth, the lens is colourless and transmits all wavelengths from follow suit, the earlier cells come to occupy a deeper position within
the infra-red to the near-ultraviolet well. However, throughout life, the the lens.


EYE
698
4
NOITCES
Lens fibres the lens. At least three varieties coexist – α, β and γ, their relative pro-
portions changing throughout life. They occur in very high concentra-
tions, and form up to 60% of the lens fibre mass. Variations in their
The inwardly displaced epithelial cells elongate further in both an
concentration in different parts of the lens give rise to regional differ-
anterior and a posterior direction, becoming up to 12 mm long,
ences in refractive index, correcting for the spherical and chromatic
depending on age and position in the lens. Fibres near the surface at
aberrations which might otherwise occur in a homogeneous lens.
the equator are nucleated; the nuclei form a short, S-shaped bow, which
extends inwards from the surface. The deeper fibres lose their nuclei
Ocular refraction
and most other organelles.
Variations in lens fibre structure and composition make it possible
to distinguish a softer cortical zone, made up of younger fibres, and a The cornea and humours have a refractive index close to that of water,
firmer central part, representing the older nucleus. The nucleus can be but the tear film covering the curved corneal surface is in contact with
further subdivided into layers representing the age at which the fibres air and therefore approximately two-thirds (approximately 40 dioptres)
within them were formed. of the refractive power of the eye is effected here. The lens has a greater
In cross-section, individual fibres are flattened hexagons measuring refractive index than the adjacent media, varying from 1.386 at its
approximately 10 µm by 2 µm. They are tightly packed, and fibres are periphery to 1.406 at its core, and contributes the remaining approxi-
firmly attached to their neighbours by a variety of mechanical junctions mately 20 dioptres of the power of the relaxed eye. The main value
(Fig. 42.18). Lens fibres are also in contact through desmosomes and of the lens is its ability to vary its dioptric power during the process of
numerous gap junctions. accommodation. Accommodation allows an increase in refraction of
All lens fibres cross a plane passing through the equator and termi- 12 dioptres in youth but this decreases with age, being halved at 40 years


nate on both the anterior and posterior lens surfaces at lens ‘sutures’. and reduced to 1 dioptre or less at 60 years (presbyopia).
These radiate out from the poles towards the equator and represent
Disorders of refraction
lines of linearly registered, interlocking junctions between terminating
lens fibres. In fetuses, the sutures on the anterior surface of the lens A relaxed eye is said to be emmetropic when the refracting structures
form a triradiate pattern centred on the anterior pole resembling the are so related to its length that the retina receives a focused image of a
limbs of an upright letter Y (Fig. 42.19A). Posteriorly, the sutural con- distant object. Although the majority of eyes are emmetropic, a large
figuration is similar but inverted. The sutures increase in number and
complexity as a consequence of lens growth and other changes in the
arrangement of lens fibres (Fig. 42.19B). Fibres that start near the
central axis of the lens anteriorly terminate posteriorly on a suture near A a
the periphery, and vice versa.
Lens fibres contain crystallins, proteins that are responsible for the
transparency and refractile properties, and for much of the elasticity, of
Capsule
Epithelium
b
B
Lens fibres
Fig. 42.19 The structure of the fetal (A) and adult (B) human lens,
showing the major details of arrangement of the lens fibres. The anterior
(a) and posterior (b) triradiate sutures are shown in the fetal lens. Fibres
pass from the apex of an arm of one suture to the angle between two
arms at the opposite pole, as shown in the coloured segments.
Ball and socket junction Tongue and groove junction
Intermediate fibres show the same reciprocal behaviour. The suture
Fig. 42.18 The mechanical junctions between lens fibres. There are no pattern becomes much more complex as successive strata are added to
junctions immediately below the epithelium. Ball and socket junctions the exterior of the growing lens, and the original arms of each triradiate
develop in deeper layers; these are subsequently eliminated towards the suture show secondary and tertiary dichotomous branchings. (With


nucleus, where tongue and groove junctions gradually form. Angle joints permission from Hogan MJ, Alvarado JA, Weddell JE 1971 Histology of
are present at most levels. the Human Eye. Philadelphia: WB Saunders.)


Retina
699
24
RETPAHC
minority have errors of refraction or ametropia that can take three dif-
ferent forms. In myopia, the eye is too long for its refractive power and
distant objects are focused in front of the retina when relaxed; closer
objects will be in focus and, consequently, the eye is said to be ‘short-
sighted’. Conversely, in hyperopia (long sight), the eye is too short for
its refractive power and, when it is relaxed, distant objects are focused
behind the retina. In astigmatism, the refractive power of the eye is not
the same in different meridians, which are approximately 90° apart in
regular astigmatism.
Normally, emmetropia is assured during development both by the
active control of the sclera’s biomechanical and biochemical properties
and changes in the optical features of the eye’s refractive elements, a
process known as emmetropization (Wallman and Winawer 2004). A
resting focal plane behind the retina results in scleral growth causing
axial elongation of the globe until the focused image and the position
of the retina are coincident. On the other hand, light focused in front
of the retina retards scleral growth, reducing axial length. In ametropia,
this process fails.
The causes of refractive errors such as myopia are both genetic and
environmental. Not only have several candidate genes been identified,
but also factors such as increased near work and lack of outdoor activity
have all been linked to myopia (Wallman and Winawer 2004, Flitcroft
2013). This has led to a recent increase in the incidence of myopia to
epidemic proportions, with a prevalence of over 80% in the adult popu-
lation of some East Asian cities (Rose et al 2008). Fortunately, errors of
refraction are amenable to correction using spectacle or contact lenses
and by various forms of refractive surgery.
Fig. 42.20A A fundus photograph of the right eye of a 19-year-old
As noted above, the ability to change the power of the lens through
Caucasian female. The central retinal vessels are seen emanating from
accommodation diminishes during the fifth decade to an extent that
the optic disc. Retinal arteries are narrower and lighter in colour, and


neither the corrected ametrope nor the emmetrope is able to focus near
generally are vitreal to the veins. The avascular centre of the macular
objects clearly, and reading spectacles become necessary. Many factors
region, with its associated macular pigment, can be seen temporal to the
could potentially cause such loss of accommodation, but it seems likely disc.
that the main cause is reduced lens elasticity with age. This is offset to
a very limited extent by the reduction of the pupil aperture with age,
which increases the depth of focus but at the cost of creating the further
RETINA
problem of requiring greater illumination.
Other errors of refraction are the concomitants of eye disease, espe-
cially those that affect the cornea. Corneal curvature, for example, may The retina is a thin sheet of cells, ranging from less than 100 µm at its
be sufficiently altered as a residual defect of past disease to cause irregu- edge to a maximum of around 300 µm at the foveal rim. It lines the
lar astigmatism. In keratoconus, the cornea is thinned and steepened inner posterior surface of the eyeball, sandwiched between the choroid
centrally, distorting the refracting surface. A dislocated lens, caused, for externally and the vitreous body internally, and terminates anteriorly at
example, by Marfan’s syndrome, also disrupts the refractive status of the ora serrata (see Fig. 42.1).
the eye. When it is viewed with an ophthalmoscope to show the fundus
oculi, the most prominent feature is the blood vessels emanating from
and entering the optic disc (Fig. 42.20A). Centred temporal and inferior
VITREOUS HUMOUR to the disc lies the ‘central retina’ or macula (diameter 5–6 mm), the
middle of which is composed of the fovea and foveola, and easily
The vitreous body occupies about four-fifths of the eyeball. Posteriorly, identified with an ophthalmoscope as an avascular area with a yellow
it is in contact with the retina, while further forwards it abuts the ciliary tinge (see Fig. 42.20A). The lack of blood vessels at the foveola is even


body, zonule and lens. Its anterior surface is hollowed into a deep more apparent in a fluorescein angiogram. The peripheral retina lies
concavity, the hyaloid fossa, fitting the shape of lens (see Fig. 42.1). It outside the central retina (Fig. 42.20B).
is colourless, consisting of approximately 99% water, but is not entirely
structureless. At its perimeter, it has a gel-like consistency (100–300 µm
thick); nearer the centre, it contains a more liquid zone. Hyaluronan, MICROSTRUCTURE
in the form of long glycosaminoglycan chains, fills the whole vitreous.
In addition, the peripheral gel or cortex contains a random loose The retina is composed of a variety of epithelial, neural and glial cell
network of type II collagen fibrils, which are occasionally grouped into types, whose distribution conventionally divides it into 10 layers (Fig.
fibres. The cortex also contains scattered cells, the hyalocytes, which 42.21). These are apparent in histological sections (Fig. 42.22), but can
possess the characteristics of mononuclear phagocytes and may contrib- also be seen in vivo using optical coherence tomography, an imaging
ute to the production of hyaluronan. While they are normally in a technique that uses backscattered light to visualize layers by differences
resting state, they have the capacity to be actively phagocytic in inflam- in their optical scattering properties (Fig. 42.23). Embryologically, the
matory conditions. Hyalocytes are not present in the cortex bordering retina is derived from the two layers of the invaginated optic vesicle.
the lens. The outer layer becomes a stratum of cuboidal pigment cells that sepa-
The liquid vitreous is absent at birth, appears first at 4 or 5 years, rates the choroid from the neural retina, and therefore forms the outer-
and increases to occupy half the vitreous space by the seventh decade. most layer of the retina: the retinal pigment epithelium (layer 1). The
Vitreous liquefaction results in an increased incidence of posterior vitre- other nine strata of the retina develop from the inner layer of the optic
ous detachment and associated floaters in the elderly. The cortex is most vesicle and form the neural retina.


dense at the pars plana of the ciliary body adjacent to the ora serrata, The outermost layer of the neural retina contains the light-sensitive
where attachment is strongest, and this is often referred to as the base parts of the photoreceptors, which convert the optical image into
of the vitreous. Apart from the vitreous base, the vitreous also has a firm neural activity. From the photoreceptors, neural activity flows radially
(peripapillary) attachment at the edge of the optic disc. This adherence to bipolar and ganglion cells, and laterally via horizontal cells in the
of the vitreous to the retina can result in traction on the retina if the outer retina and amacrine cells in the inner retina. Photoreceptors
vitreous shrinks, such as occurs in old age, resulting in macular holes synaptically contact each other and bipolar and horizontal cells in the
or peripheral breaks, possibly leading to retinal detachment. outer plexiform layer (layer 5), while bipolar, amacrine and ganglion
A narrow hyaloid canal runs from the optic nerve head to the central cells synapse in the inner plexiform layer (layer 7). The axons of
posterior surface of the lens (see Fig. 42.1). In the fetus, this contains ganglion cells run towards the optic disc in the nerve fibre layer
the hyaloid artery, which normally disappears about 6 weeks before (layer 9), where they leave the retina as the optic nerve, which trans-
birth. The canal persists in adult life as a very delicate fibrous structure mits the retinal output to the visual areas of the brain where visual
and is of no functional importance. processing is completed. Although most neural activity flows from the


Eye
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RETPAHC
Fig. 42.20B Fluorescein angiogram showing the macular region of a right
eye. The main macular vessels are approaching from the right. The
subject was an elderly person with considerable macular pigmentation,
which masks fluorescence from the choroidal circulation.


EYE
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Astrocyte
Internal limiting
membrane
Nerve fibre layer
Ganglion cell layer Retinal ganglion cell
Inner plexiform layer
Displaced amacrine cell
Bipolar cell
Inner nuclear layer Müller cell
Amacrine cell
Horizontal cell
Outer plexiform layer
External limiting
Outer nuclear layer membrane
Cell bodies of rods and cones
Cone
Photoreceptor cell inner
Rod
and outer segments
Pigment epithelium
Choroid
Fig. 42.21 Neural cells whose cell bodies and interconnections account for the layered appearance of the retina in histological section (compare with
Fig. 42.22). Also shown are the two principal types of neuroglial cell in the retina (although microglia are also present, they are not shown).
10 Foveola Papillomacular bundle Optic nerve head
9
8
7 GCL NFL
IPL
6 ELM INL OPL
IS/OS ONL
5
RPE/CH
4
3
2
1
CC
500 µm 100 µm
Fig. 42.23 A high-definition optical coherence tomography (OCT) in vivo
SC image of the human retina. The image has approximately 2 µm axial
resolution, is 8 mm long and consists of 10,000 axial scans. The image is
Fig. 42.22 A transverse section of the retina and choroid. The 10 layers
expanded in the vertical direction to permit better visualization of retinal
of the retina are shown. Key: 1, pigment epithelial layer; 2, rod and cone
layers. Abbreviations: ELM, external limiting membrane; GCL, ganglion
layer; 3, external limiting membrane; 4, outer nuclear layer; 5, outer
cell layer; INL, inner nuclear layer; IPL, inner plexiform layer; IS/OS,
plexiform layer; 6, inner nuclear layer; 7, inner plexiform layer; 8, ganglion
boundary between the photoreceptor inner and outer segments; NFL,
cell layer; 9, nerve fibre layer; 10, internal limiting membrane.
nerve fibre layer; ONL, outer nuclear layer; OPL, outer plexiform layer;
Abbreviations: CC, choriocapillaris; SC, suprachoroid.


RPE/CH, retinal pigment epithelium and choriocapillaris. (Courtesy of
Professor James Fujimoto, Department of Electrical Engineering and
Computer Science, MIT, Boston, USA.)
photoreceptors towards the brain, some information flow occurs in the
opposite direction via centripetal fibres in the optic nerve and inter-
plexiform cells in the retina that connect the inner and outer plexiform
Cells of the retina
layers.
The classic 10-layered appearance of the retina is absent in the optic
nerve head, the fovea and foveola, and the ora serrata. At the optic Retinal pigment epithelium
nerve head, the axons of the retinal ganglion cells leave the retina to The retinal pigment epithelium is composed of approximately cuboidal
form the optic nerve and all the other neural cell types are missing. At cells that form a single continuous layer extending from the periphery
the fovea and foveola, the inner five layers of the retina are ‘pushed of the optic disc to the ora serrata, where it continues as the outer ciliary
aside’. At the ora serrata, where the retina borders the ciliary body (see epithelium. The cells are flat in radial section and hexagonal or pen-
Fig. 42.10), the retinal pigment epithelium merges with the outer pig- tagonal in surface view, and number 4–6 million in the human retina.
mented epithelium of the ciliary body, while the neural retina borders Their cytoplasm contains numerous melanosomes. Apically (towards
the inner unpigmented ciliary epithelium; the retina is thinnest at this the rods and cones), the cells bear long (5–7 µm) microvilli that
point. The normal layered arrangement of the neural retina approach- contact, or project between, the outer segments of rods and cones. The
ing the ora serrata is frequently disrupted by cysts in older individuals tips of rod outer segments are deeply inserted into invaginations in
(Fig. 42.24). the apical membrane of the retinal pigment epithelium. The different


Retina
701
24
RETPAHC
embryological origins of the retinal pigment epithelium and neural Retinal pigment epithelium cells play a major role in the turnover
retina mean that the attachments between these two layers are unsup- of rod and cone photoreceptive components. Their cytoplasm contains
ported by junctional complexes; the neural retina and retinal pigment the phagocytosed tips of rods and cones undergoing lysosomal destruc-
epithelium are therefore easily parted (retinal detachment) due to tion. The final products of this process are lipofuscin granules, which
trauma or disease. accumulate in these cells with age. Disturbances in this phagocytic
activity of the retinal pigment epithelium can lead to retinal disease
Ora serrata Retinal cyst (Kevany and Palczewski 2010).
Light reaching the outer retina but missing the photoreceptors is
absorbed by the retinal pigment epithelium, which, like melanin else-
where in the eye, prevents such stray light degrading image quality. The
zone of tight junctions between adjacent cells also allows the epithe-
lium to function as an important blood–retinal barrier between the
retina and the vascular system of the choroid. The retinal pigment epi-
thelium is required for the regeneration of bleached visual pigment and
may have antioxidant properties. It also secretes a variety of growth
factors necessary for the integrity of the choriocapillaris endothelium
and the photoreceptors, and produces a number of immunosuppressive
factors. A failure of any of the diverse functions of the retinal pigment
epithelium could result in compromised retinal function and eventual
Unpigmented epithelium of Pigmented epithelium of Retinal pigment epithelium blindness (Strauss 2005).
ciliary body ciliary body
Rods and cones
Fig. 42.24 The junction between the retina and ciliary body (ora serrata).
The retinal pigment epithelium is continuous with the outer, pigmented Rods and cones are the ‘image-forming’ photoreceptors of the outer
epithelium of the ciliary body, while the neural retina abuts the inner, retina and function at low (scotopic) and higher (photopic) light levels,


unpigmented epithelium of the ciliary body. The layered appearance that respectively. Both are long, radially orientated structures with a similar
is apparent elsewhere in the neural retina is disrupted adjacent to the ora organization, although details differ (Fig. 42.25). From the choroidal
serrata by cystic degeneration. end inwards, the cells consist of outer and inner segments connected
A B Fig. 42.25 The major features of a
retinal rod cell (A) and a retinal cone
cell (B). The relative size of the
pigment epithelial cells has been
Lateral process exaggerated for illustrative purposes.
Rod spherule with gap junction
Cone pedicle
Müller cell
cytoplasm
Cell body
and nucleus
Cell body
and nucleus
Myoid
Inner segment
Müller cell microvilli
Ellipsoid
Centriole
Cilium Calycal process
Cone lamellae
Rod lamellae Pigment
epithelial
microvilli Outer segment
Phagosomal
vacuole
Pigment
granule
Pigment
epithelial Pigment
cell epithelium
Bruch’s
membrane


EYE
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NOITCES
by a thin connecting cilium (together making up layer 2 of the retina), populations of cones absorbing maximally at the short- (λ 420 nm),
max
a cell body containing the nucleus, and a synaptic terminal (either a middle- (λ 534 nm) and longer-wave (λ 563 nm) end of the
max max
more complex pedicle for cones or a simpler rod spherule) where they visible spectrum. The three cone classes are sometimes referred to as
make synaptic connections with adjacent bipolar and horizontal cells the blue, green and red cones but are better classed as S, M and L cones.
and with other cone or rod cells within the outer plexiform layer. The action of light is to isomerize the retinal, separating it from the
The nuclei of the rods and cones form the outer nuclear layer (layer opsin, a process which, via a G-protein coupled enzyme cascade and a
4). The cone nuclei are relatively large and oval, and generally form a second messenger system, results in the closure of cation channels in
single layer that often penetrates the external limiting membrane (layer the receptor outer segment membrane, a hyperpolarization of the
3). They also contain less heterochromatin and thus usually stain more photoreceptor, and a consequent decrease in the release of the neuro-
lightly. Rod nuclei are round and smaller, stain more darkly, and form transmitter glutamate from its synapses.
several layers vitreal to the cone nuclei. The human retina contains, on average, 4.6 million cones and
The external limiting is not, in fact, a membrane at all, although it 92 million rods, although there is significant inter-individual variation
appears as such in the light microscope; rather, it is a series of zonulae (Curcio et al 1990). Although cones populate the whole retina, their
adherentes between photoreceptors and the glial (Müller) cells that density is highest in the foveola, where approximately 7000 cones reach
separate them. These junctions most likely serve to anchor the photo- an average density of 199,000 cones/mm2; this area is entirely rod-free.
receptors and prevent leakage of the interphotoreceptor matrix that Going outwards from the foveola, rod numbers rise, reaching a peak


surrounds the photoreceptor outer and inner segments. density in a horizontal elliptical ring at the eccentricity of the optic disc,
Rod outer segments are cylindrical and consist of around 1000 flat- before declining once more towards the periphery. Cone density is
tened, lobulated, membranous discs. These form as deep infoldings of 40–45% higher in the nasal compared to the temporal retina, and
the plasma membrane at the base of the outer segment; they ‘bud off’ slightly higher inferiorly than superiorly.
after formation so that the discs are not attached to the plasma mem- The number of S cones in all human retinae is similar, making up
brane and are free-floating within the outer segment. Cone outer seg- less than 10% of all cones (Curcio et al 1991, Hofer et al 2005). The
ments are generally shorter and, as their name implies, often conical distribution of S cones is relatively even throughout the retina, although
(especially in the peripheral retina). Cone discs do not bud off after they are absent from the central fovea. The relative proportions of L and
formation and remain as infoldings of the plasma membrane. M cones shows a much greater degree of variation between individuals,
The inner segment of both rods and cones is divided into an outer, the L : M cone ratio varying from close to unity to over 10. The distribu-
mitochondria-rich, ellipsoid and an inner myoid that contains endo- tion of L and M cones is more irregular than that of S cones, and appears
plasmic reticulum. In most of the retina, these inner segments are random with some indication of clumping (Bowmaker et al 2003,
much wider in cones (5–6 µm at their widest point) than rods (1.5 µm) Hofer et al 2005).
(Fig. 42.26). In both rods and cones, proteins are manufactured within The high packing density of cones at the foveola, achieved by de-
the myoid and incorporated into the newly formed discs at the base of creasing inner segment size, ensures maximal resolution, while the
the outer segment. In rods, as new discs are added, and old discs are presence of more than one spectral cone type allows colour vision. S


pushed up the outer segment and eventually phagocytosed by the cones probably contribute little to spatial resolution because they are
retinal pigment epithelium. Cone discs are also phagocytosed but the absent from the foveola. Rod-based vision provides high sensitivity, but
incorporation of new proteins within the discs is more diffuse (Nguyen- with relatively low spatial discrimination and no ability to distinguish
Legros and Hicks 2000). While all rods within the retina have a similar wavelengths. Although many of the functional differences between rods
structure, the cones at the foveola are highly modified compared to and cones rely on the different properties of the photoreceptors them-
those situated more peripherally and, in many ways, resemble rods selves, their connectivity to other retinal neurones is equally important.
with a longer outer segment and a thinner inner segment.
Light is absorbed by rhodopsins, visual pigments consisting of a Horizontal cells
protein, opsin, that spans the membrane of the outer segment discs, Horizontal cells are inhibitory interneurones. Their dendrites and axons
bound to a light-absorbing chromophore, retinal, which is an aldehyde extend laterally within the outer plexiform layer, making synaptic con-
of vitamin A. Such rhodopsins have a smooth, bell-shaped absorption tacts with cone pedicles and rod spherules, and, via gap junctions at
1
profile with a point of maximum absorbance (λ ), indicating the the tips of their dendrites, with each other. Their cell bodies lie in the
max
wavelength at which they are most sensitive. Humans possess four dif- outer part of the inner nuclear layer (layer 6). Three morphological
ferent opsins, resulting in four spectrally distinct visual pigments: one types of horizontal cell can be distinguished in the human retina (Kolb
located within the rods (λ 498 nm) and three within different et al 1992). The dendrites of HI and HIII cells contact cones, and their
max
axons terminate on rods. Both the axons and dendrites of HII cells
synapse only with cones.
Bipolar cells
Bipolar cells are radially orientated neurones. Their dendrites synapse
on photoreceptors, horizontal cells and interplexiform cells in the outer
plexiform layer. Their somata are located in the inner nuclear layer, and


axonal branches in the inner plexiform layer synapse with dendrites of
ganglion cells or amacrine cells. Golgi staining has identified nine dis-
tinct types of bipolar cell in the human retina (Kolb et al 1992), eight
of which contact cones exclusively, and the remaining type synapses
only on rods.
Cone bipolars are of three major morphological types: midget, S
(blue) cone and diffuse, according to their connectivity and size. Midget
cone bipolar cells either invaginate the cone pedicle or synapse on its
base (flat subtype). In the central retina, each midget bipolar cell con-
tacts only a single cone (2–3 in the periphery), forming part of a one-
to-one channel from cone to ganglion cell that mediates high spatial
resolution. S cones form part of a short-wavelength mediating channel,
while the larger diffuse cone bipolars are connected to up to 10 cones
and are thought to signal luminosity rather than colour.
Cone bipolar cells can also be of two physiological types, according
Fig. 42.26 A tangential section of a human retina in the parafovea cut at
to their response to the light-induced decrease in glutamate release from
the level of the inner/outer segments, showing the ‘mosaic’ of both the
the photoreceptors to which they are synaptically connected. If illumi-
larger cones and the more numerous, but smaller, rods. Photoreceptors
nation of the photoreceptors with a point of light causes a depolariza-
at the top of the image are sectioned at a level closer to the retinal
tion of the connected bipolar cell, it is said to be an ‘ON’ bipolar,
pigment epithelium than receptors lower in the figure. The reduction in
size of the cones at the top of the figure is explained by the conical contacting the cone by ‘sign-inverting’ synapses with metabotropic
shape of their outer segment. If the figure were continued upwards, receptors. However, if cones are connected to an ‘OFF’ bipolar cell via
representing sections closer to the retinal pigment epithelium, the size of ‘sign-conserving’ synapses with ionotropic receptors, illumination of
the cones would continue to decrease and the amount of surrounding the photoreceptor will result in hyperpolarization of the bipolar cell.


white space would increase. Rod outer segment diameter, however, Illumination of a concentric area of surrounding photoreceptors causes
would change little. the opposite response in bipolar cells to illumination within their


Retina
703
24
RETPAHC
dendritic field. This inhibition is mediated via horizontal cells and gives layer. Ganglion cell bodies, together with displaced amacrine cells, form
rise to the antagonistic centre-surround type receptive field that is char- the ganglion cell layer of the retina (layer 8). Throughout most of the
acteristic of all levels of the visual system up to and including the retina, they form a single layer; they become progressively more numer-
occipital cortex. ous near the macula, where they are ranked in up to 10 rows, reaching
The single morphological type of rod bipolar cell contacts 30–35 a peak density of up to 38,000/mm2 in a horizontally orientated ellipti-
rods in the central retina, increasing to 40–45 rods in the periphery. cal ring 0.4–2.0 mm from the foveal centre. Their number diminishes
Such convergence serves to increase the absolute sensitivity of the rod again towards the fovea, from which they are almost totally excluded.
system. All rod bipolar cells are ‘ON-centre’ and do not contact ganglion Up to 15 ganglion cell types have been identified in the mammalian
cells directly, but synapse with a class of amacrine cell (AII), which then retina based on morphology, physiology, and target area in the brain,
contacts cone bipolar cells. each of them presumably functionally distinct. For example, some
The inner plexiform layer can be divided into two main layers: an project to different regions of the lateral geniculate nucleus and form
outer layer containing the synaptic endings of ‘OFF’ cone bipolar cells, three parallel visual pathways involved in conscious visual perception,
and an inner layer of ‘ON’ cone and rod bipolar cell synapses. namely: the magnocellular and parvocellular systems and a pathway
carrying the S cone signal (Wässle 2004). Midget ganglion cells (P cells)
Amacrine cells contact only single midget bipolar cells in the central retina, which, in
Most amacrine cells lack typical axons and, consequently, their den- turn, connect to single cones, giving each cone a ‘private line’ out of the
drites make both incoming and outgoing synapses. Each neurone has retina and ensuring optimal acuity. The large dendritic field of parasol


a cell body either in the inner nuclear layer near its boundary with the cells (M cells) is consistent with a role in motion detection. Parasol and
inner plexiform layer, or on the outer aspect of the ganglion cell layer, midget ganglion cells together make up around 80% of human retinal
when it is known as a displaced amacrine cell. The processes of ama- ganglion cells. The remaining cells (approximately 200,000) project to
crine cells make a variety of synaptic contacts in the inner plexiform the superior colliculus of the midbrain, the thalamic pulvinar, the pre-
layer with bipolar and ganglion cells, as well as with other amacrine tectum and the accessory optic system, and contribute to various sub-
cells. conscious visual reflexes such as the pupillary and accommodation
The various classes of amacrine cell serve a number of important responses (see Fig. 42.12). In addition, a population of around 3000
functions. AII cells play an essential role in the rod pathway (see above). large, intrinsically light-sensitive ganglion cells form a network com-
Other cells appear to be important modulators of photoreceptive posed of extensive overlapping dendrites (Dacey et al 2005). Such
signals, and serve to adjust or maintain relative colour and luminosity ‘inner retinal photor eceptors’ contain a retinal-based visual pigment
inputs under changing light conditions. They are probably also respon- (melanopsin; λ 479 nm), which resembles an invertebrate-type
max
sible for some of the complex forms of image analysis known to occur visual pigment in many of its characteristics. These light-sensitive gan-
within the retina, such as directional movement detection. Up to 24 glion cells are part of a pathway parallel to the rod- and cone-mediated
different morphological types are recognized in humans (Kolb et al ‘image-forming’ system that monitors overall levels of illumination.
1992); coupled to their neurochemical complexity, this makes them This ‘non-imaging’ pathway is the major route by which the eye influ-
perhaps the most diverse neural cell type in the body. ences circadian rhythms via the suprachiasmatic nucleus; it also con-
tributes to light-evoked pupillary constriction via projections to the
Interplexiform cells olivary pretectal nucleus. Although the axons of some of these photo-


Interplexiform cells, often regarded as a subclass of amacrine cells, sensitive ganglion cells also project to the lateral geniculate nucleus,
generally have cell bodies in the inner nuclear layer. They are postsyn- their wider contribution to conscious visual perception remains incom-
aptic to cells in the inner retina, and send signals against the general pletely understood.
direction of information flow in the retina, synapsing with bipolar, Ganglion cell axons, which form the nerve fibre layer on the inner
horizontal and photoreceptor cells in the outer plexiform layer. surface of the retina, run parallel to the surface of the retina, and con-
Although their function is uncertain, it is likely that, through the release verge on the optic nerve head where they leave the eye as the optic nerve.
of γ-aminobutyric acid (GABA) and dopamine, they adjust some aspect Fibres from the medial (nasal) retina approach the disc in a simple
of retinal function such as sensitivity. radial pattern (Fig. 42.27), whereas axons from the lateral (temporal)
retina take an arcuate route as they avoid the fovea. Axons from the
Ganglion cells
macula form a papillomacular fasciculus that passes almost straight to
The human retina contains 0.7–1.5 million ganglion cells, the output the disc. The thickness of the nerve fibre layer increases dramatically
neurones of the retina (Curcio and Allen 1990). Their dendrites synapse near the optic disc as fibres from the peripheral retina traverse more
with processes of bipolar and amacrine cells in the inner plexiform central areas. Towards the edge of the disc, the other retinal layers thin,
Temporal side Nasal side of Fig. 42.27 Directions of axons (dashed lines) and
of optic disc optic disc blood vessels of the nerve fibre layer of the retina
of the right eye. Axons pass radially on the nasal
side of the optic disc, whereas fibres on the
temporal side avoid crossing the fovea by arching
around it. Some of the fibres from the fovea and
central region pass straight to the optic disc and
others arch above and below the horizontal;
together, these form the papillomacular bundle. A
Raphe
raphe is formed by the central fibres temporal to
the fovea. Venules are shown crossing in front of


Fovea
arteries; the reverse relationship is probably the
Papillomacular more common pattern. All vessels issue from the
bundle disc on the right of the figure; the larger temporal
branches tend to arch around the central region
of the retina and do not approach the fovea. The
peripheral retina and most of the nasal retina are
not shown.


EYE
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and, at the disc, all neural elements of the retina other than ganglion
cell axons are excluded.
Axons of ganglion cells are surrounded by the processes of radial
glial cells and retinal astrocytes, and are almost always unmyelinated
within the retina, which is an optical advantage because myelin is
refractile. Although a few small myelinated axons may occur, myelin-
ation does not generally start until axons enter the optic disc to become
the optic nerve.
Retinal glial cells
There are three types of retinal glial cells: radial Müller cells, astrocytes
and microglia. Müller cells form the predominant glial element of the
retina; retinal astrocytes are largely confined to the ganglion cell and
nerve fibre layers; and microglial cells are scattered throughout the
neural part of the retina in small numbers.
Müller cells span almost the entire thickness of the neural retina,
ensheathing and separating the various neural cells except at synaptic
sites. They constitute much of the total retinal volume, and almost
totally fill the extracellular space between neural elements. Their nuclei
lie within the inner nuclear layer, and from this region each cell body
extends a single thick fibre that runs radially outwards, giving off Fig. 42.28 A section through the fovea centralis. (With permission from
Young B, Heath JW 2000 Wheater’s Functional Histology. Edinburgh:
complex lateral lamellae that branch among the processes of the outer
Churchill Livingstone.)
plexiform layer. Apically, each central process terminates at the external
limiting membrane, from which microvilli project for a short distance
into the space between the rod and cone inner segments (fibre baskets)
(see Fig. 42.25). On the inner surface of the retina, the main Müller cell
process expands into a terminal foot plate that contacts those of neigh- fovea. The Henle fibres contain two xanthophyll carotenoid pigments
bouring glial cells and forms part of the internal limiting membrane (lutein and zeaxanthin), which create an elliptical yellowish area
(see below). (approximately 2 mm horizontally and 1 mm vertically): the macula


The functions of Müller cells are numerous (Reichenbach and Bring- lutea. Macular pigment density varies by more than an order of magni-
mann 2013). Like astrocytes, Müller cells contact blood vessels, espe- tude between individuals, is influenced by several environmental
cially capillaries of the inner nuclear layer, and their basal laminae fuse factors, including diet, and is negligible in the central foveola. Low
with those of perivascular cells or vascular endothelia, contributing to levels of macular pigment are likely to be associated with retinal path-
the formation of the blood–retinal barrier. They also maintain the ologies such as age-related macular degeneration (Beatty et al 2008).
stability of the retinal extracellular environment by, for example, regula- The absence of the inner retinal layers, including blood vessels (see
tion of K+ levels, uptake of neurotransmitter, removal of debris, storage Fig. 42.20A), reduces light scatter, which, along with the increased
of glycogen, providing neuroprotective support to the photoreceptors packing density of cones in the foveola and their lack of convergence
and mechanical support to the whole neural retina. Recently, it has been with ganglion cells, ensures that visual resolution is highest in this part
shown that they are also involved in the regeneration of cone visual of the retina. Acuity may be further enhanced by the macular pigment,
pigments, that some are a source of stem cells and that they may even which, apart from having antioxidant properties and removing poten-
act as light guides, conveying light from the inner retina to the photo- tially harmful short-wave radiation, will absorb those wavelengths most
receptors and overcoming some of the optical disadvantages of an prone to chromatic aberration and Rayleigh scatter.
‘inverted’ retina.
The cell bodies of retinal astrocytes lie within the nerve fibre layer
VASCULAR SUPPLY
and their processes branch to form sheaths around ganglion cell axons.
The close association between astrocytes and blood vessels in the inner
retina suggests that they contribute to the blood–retinal barrier. Retinal The retina has a dual arterial supply and both parts are necessary to
microglia are scattered mostly within the inner plexiform layer. Their maintain retinal function. The outer five layers of the retina are avascu-