Light effects on circadian rhythm collected by rod cells and cone cells and the retinal ganglion cells (RGCs), or it is directly collected by these RGCs. The RGCs use the photopigment melanopsin to absorb the light energy. Specifically, this class of RGCs being discussed is referred to as "intrinsically photosensitive," which just means they are sensitive to light. There are five known types of intrinsically photosensitive retinal ganglion cells (ipRGCs): M1, M2, M3, M4, and M5. Each of these differently ipRGC types have different melanopsin content and photosensitivity. These connect to amacrine cells in the inner plexiform layer of the retina. Ultimately, via this retinohypothalamic
Gene therapy of the human retina and RPE layer, in a short surgical procedure. Although this is more invasive than the intravitreal route, the fluid is absorbed by the RPE and the retina flattens in less than 14 hours without complications. Intravitreal AAV targets retinal ganglion cells and a few Muller glial cells. Subretinal AAV efficiently targets photoreceptors and RPE cells. The reason that different routes of administration lead to different cell types being transfected (e.g., different tropism) is that the inner limiting membrane (ILM) and the various retinal layers act as physical barriers for the delivery of drugs and vectors to the deeper retinal layers.