over 50 million people suffer from cataracts and the number will increase as populations of the current generation grow older .
currently , the only treatment for cataracts is the surgical removal of the opaque lenses and substitution with clear ones .
intraocular lens implantation is verified to be the most effective method to treat cataract , but it involves risks such as irreversible impairments of vision , retinal detachment , and endophthalmitis .
surgery is not equally available to all patients and an artificial lens does not always attain the overall optical qualities of a normal lens .
therefore , preventing or delaying the onset of cataract by pharmacological approaches may lessen this burden , reduce the occurrence of blindness , and enhance the quality of life for older populations .
overwhelming evidence indicates that oxidative stress is involved in the pathophysiology of a wide variety of human diseases , including cancer , cardiovascular disease , acquired immune deficiency syndrome ( aids ) , diabetes mellitus , and neurodegenerative disorders such as aging , parkinson s disease , and alzheimer s disease . recently , both epidemiological and experimental studies have provided evidence that the oxidative stress is a critical mechanism responsible for the initiation and progression of cataracts . the term oxidative stress has been defined as a disturbance in the equilibrium status of oxidant / antioxidant systems with progressive accumulating of reactive oxygen species ( ros ) in intact cells .
lens epithelium cells ( lec ) are the center of metabolic activities in lenses , and the oxidative stress on lec significantly contributes to the pathogenesis of cataracts .
ros serve as cellular signaling molecules . however , at high concentrations , ros may give rise to both beneficial and unbeneficial effects . in the latter case ,
ros may not only kill invading pathogens and microbes , but also damage the components of the cell , including proteins , lipids , carbohydrates , and dna . in the eye , ros subtypes such as the hydroxyl radicals ( oh ) and the peroxynitrite ( onoo ) can attack the aforementioned biological molecules , leading to lipid peroxidation and depletion of the antioxidant enzymes superoxide dismutase ( sod ) and glutathione ( gsh ) , which further exacerbate oxidative stress .
ros is mostly generated within the mitochondria in lens epithelium cells and the superficial fiber cells , which are highly reactive and can damage macromolecules in living cells , such as lipids , proteins , and nucleic acids , causing mutagenesis and cell death .
these ros significantly contribute to the pathogenesis of many ophthalmological disorders including cataract , and are neutralized by presence of endogenous antioxidants in the eye .
however , if the endogenous antioxidant system is not potent enough to counter excessive oxidative stress , the surplus ros inevitably gives rise to impairment of the lens .
it has been confirmed that ros which mediate the formation of cataract are mostly brought about by age .
accordingly , lenses have evolved antioxidant systems to defend against the toxic ros via endogenous or exogenous antioxidants , such as gsh , and sod , catalase ( cat ) , glutathione s - transferase ( gst ) , and glutathione reductase / peroxidase ( gr / gpx ) .
molecular hydrogen is a colorless , odorless , nonmetallic , tasteless , highly flammable diatomic gas which was first documented by philippus aureolus paracelsus in 1520 as a kind of flammable gas . in 2007 , ohsawa et al . found that molecular hydrogen could selectively reduce cytotoxic reactive oxygen species in vitro and thereby exert therapeutic antioxidant activity . from then on , research on hydrogen set off a worldwide upsurge in research interest [ 2226 ] .
hydrogen has been shown to exert protective effects on transplantation - induced intestinal graft injury , chronic liver inflammation , and vestibular hair cells , as well as regional myocardial ischemia and reperfusion .
intriguingly , hydrogen does not disturb the metabolic oxidation - reduction reactions , innate immune system , or physiologic parameters .
it has been found that hydrogen selectively quenches detrimental ros such as oh and onoo , while maintaining metabolic oxidation - reduction reaction and other less potent ros , such as superoxide anion radical ( o2 ) , hydrogen peroxide ( h2o2 ) , and nitric oxide ( no ) .
hydrogen gas can penetrate biomembranes , diffuse into the cytosol , mitochondria , and nucleus , and protect cells and tissues against oxidative stress by scavenging ros . especially in humans
, the fact that the amount of hydrogen dissolved in venous blood is less than that in artery blood suggests that hydrogen can penetrate most membranes and diffuse into organelles .
it was supposed that the elevated hydrogen level in serum might lead to the incorporation of hydrogen into organs , and thus control the oxidative stress - induced tissue damage . on the other hand , hydrogen as a natural molecule
. however , hydrogen inhalation is not convenient and may be dangerous because it is inflammable and explosive if the concentration of hydrogen in the air is greater than 4% .
hydrogen can be dissolved in water up to 0.8 mm under atmospheric pressure at room temperature and its solubilized form , the hydrogen - rich saline ( hrs ) , is advantageous since it is a safe , portable , and easily handled approach for delivery .
the hrs can be administered by drinking , or by peritoneal or intravenous injections , and has shown effective therapeutic effects on oxidative stress in several models : both in vitro and in vivo studies have verified that the antioxidant properties of hrs can decrease the incidence of ros - related diseases .
studies from other laboratories have proven that hrs provides protection against oxidative damage induced by ischemia / reperfusion in lung , intestinal , liver , and brain [ 3941 ] .
it was also then used to improve the quality of life of patients clinically treated with radiotherapy for liver tumors .
previous studies indicated that disruption of the balance between ros production and scavenging leads to human lens epithelial ( hle ) cell apoptosis , which is closely associated with cataract formation .
therefore , the cellular antioxidant defense system has been proposed as an important factor in protecting hle cells against oxidative stress and postponing cataract formation .
the system includes oxygen eliminators such as gsh , sod , cat , gpx , gr , and gst , which protect the crystallins from oxidative damage
. however , their active oxygen - scavenging activities are not potent enough to counteract cataract formation in the lens .
therefore , it may be necessary and reasonable to supply exogenous antioxidants to suppress oxidative damage to the lens proteins .
administration of hrs might provide a higher concentration of hydrogen and a better spread of hydrogen into the hle cell , scavenging the toxic ros in the aged lens , and thereby acting as an innovative therapy against cataracts .
it is a logical step to verify the therapeutic effects of hrs on various models of cataract , and eventually apply them in the treatment of cataract patients .
under physiological conditions , ros are products of normal oxygen metabolism and have beneficial biological effects at low concentrations , but higher levels of ros can harm the body . external environmental factors ( e.g. , heat , uv light , x and gamma radiation , and therapeutic drugs ) , behavioral activities ( e.g. , smoking , long - duration exercise ) and inflammatory cells ( e.g. , activated macrophages and neutrophils ) can trigger the release various ros ( e.g. , h2o2 , no , o2 , ho , and hocl ) . although ros have extremely short half - lives , they can cause substantial damage to tissues and cellular components .
some ros , such as superoxide anion and h2o2 , can be detoxified by antioxidant defense enzymes , but there has been no information about enzymes that can detoxify oh and onoo , which are extremely reactive free radicals in cells since they can easily react with cellular macromolecules to exert a strong cytotoxic effect , until a recent study reported that hydrogen gas can selectively reduce these 2 harmful free radicals .
hydrogen reacts only with the strongest oxidants ( oh and onoo ) , which is advantageous for medical procedures , since it is mild enough not to disturb metabolic oxidation - reduction reactions or disrupt ros involved in cell signaling . moreover , the hydrogen molecule is electronically neutral and has the ability to penetrate the membranes of cell , nucleus , and mitochondria .
recently , the application of hydrogen - rich saline ( hrs ) represents an alternative model of delivering molecular hydrogen , and it may be of potential therapeutic value in the treatment of oxidative stress - associated pathologies . in the cells of the eye , ros can initiate a surge of toxic biochemical reactions , such as peroxidation of the membrane lipids and extensive damage of the proteins , which cause intracellular protein aggregation and precipitation . accordingly , oxidative stress is believed to play a pivotal role in cataract formation .
it is well known that damage to hle cells is an early event in cataract development , and hle cell apoptosis is suggested as a crucial cause of cataract formation .
the administration of hrs has been shown to be beneficial for several ophthalmological pathologies , such as reducing retinal ischemia , protecting against glutamate - induced retinal injury and the hyperoxia - induced retinal neovascularization , inhibiting corneal neovascularization caused by alkali burn , and preventing diabetic retinopathy .
hrs can be administered by drinking , or by peritoneal , intravenous , or subcutaneous injection .
therefore , it is reasonable and interesting to investigate whether molecular hydrogen has a potential therapeutic value for cataractogenesis .
recent pioneering studies represent an early attempt to evaluate the potential therapeutic effects of antioxidants against cataract formation .
the results suggest that hrs could reduce cataract formation and restore antioxidant capacity in the selenite - induced cataract model .
the potential clinical use in cataract patients relies on providing a safe source of hydrogen and exact curative effect analysis .
we can not determine the optimal hydrogen treatment dose without confirming the treatment to be safe and effective .
therefore , our hypothesis needs to be translated into effective treatment strategies for patients . considering the characteristics of the slow development of cataract , assessing the
large - scale , randomized , controlled , double - blind clinical trials are needed to determine the clinical feasibility of hydrogen treatment .
 cataract is the leading cause of irreversible blindness worldwide . 
 increasing evidence indicates that oxidative stress is an important risk factor contributing to the development of cataract . 
 moreover , the enhancement of the antioxidant defense system may be beneficial to prevent or delay the cataractogenesis . 
 the term oxidative stress has been defined as a disturbance in the equilibrium status of oxidant / antioxidant systems with progressive accumulation of reactive oxygen species ( ros ) in intact cells . 
 superfluous ros can damage proteins , lipids , polysaccharides , and nucleic acids within ocular tissues that are closely correlated with cataract formation . 
 therefore , prevention of oxidative stress damage by antioxidants might be considered as a viable means of medically offsetting the progression of this vision - impairing disease . 
 molecular hydrogen has recently been verified to have protective and therapeutic value as an antioxidant through its ability to selectively reduce cytotoxic ros such as hydroxyl radical ( oh ) . 
 hitherto , hydrogen has been used as a therapeutic element against multiple pathologies in both animal models and human patients . unlike most well - known antioxidants , which are unable to successfully target organelles 
 , hydrogen has advantageous distribution characteristics enabling it to penetrate biomembranes and diffuse into the cytosol , mitochondria , and nucleus . 
 consequently , we speculate that hydrogen might be an effective antioxidant to protect against lens damage , and it is important to further explore the biological mechanism underlying its potential therapeutic effects . 
Background
Our Hypothesis
The Feasibility of the Hypothesis
Conclusions