Cataracts, one of the leading causes of preventable blindness worldwide, refers to lens degradation that is characterized by clouding, with consequent blurry vision. As life expectancies improve, the number of people affected with cataracts is predicted to increase worldwide, especially in low-income nations with limited access to surgery. Although cataract surgery is considered safe, it is associated with some complications such as retinal detachment, warranting a search for cheap, pharmacological alternatives to the management of this ocular disease. The lens is richly endowed with a complex system of non-enzymatic and enzymatic antioxidants which scavenge reactive oxygen species to preserve lens proteins. Depletion and/or failure in this primary antioxidant defense system contributes to the damage observed in lenticular molecules and their repair mechanisms, ultimately causing cataracts. Several attempts have been made to counteract experimentally induced cataract using in vitro, ex vivo, and in vivo techniques. The majority of the anti-cataract compounds tested, including plant extracts and naturally-occurring compounds, lies in their antioxidant and/or free radical scavenging and/or anti-inflammatory propensity. In addition to providing an overview of the pathophysiology of cataracts, this review focuses on the role of various categories of natural and synthetic compounds on experimentally-induced cataracts.

Ocular health has emerged as one of the major issues of global health concern with a decline in quality of life in an aging population, in particular and rise in the number of associated morbidities and mortalities. One of the chief reasons for vision impairment is oxidative damage inflicted to photoreceptors in rods and cone cells by blue light as well as UV radiation. The scenario has been aggravated by unprecedented rise in screen-time during the COVID and post-COVID era. Lutein and Zeaxanthin are oxygenated carotenoids with proven roles in augmentation of ocular health largely by virtue of their antioxidant properties and protective effects against photobleaching of retinal pigments, age-linked macular degeneration, cataract, and retinitis pigmentosa. These molecules are characterized by their characteristic yellow-orange colored pigmentation and are found in significant amounts in vegetables such as corn, spinach, broccoli, carrots as well as fish and eggs. Unique structural signatures including tetraterpenoid skeleton with extensive conjugation and the presence of hydroxyl groups at the end rings have made these molecules evolutionarily adapted to localize in the membrane of the photoreceptor cells and prevent their free radical induced peroxidation. Apart from the benefits imparted to ocular health, lutein and zeaxanthin are also known to improve cognitive function, cardiovascular physiology, and arrest the development of malignancy. Although abundant in many natural sources, bioavailability of these compounds is low owing to their long aliphatic backbones. Under the circumstances, there has been a concerted effort to develop vegetable oil-based carriers such as lipid nano-emulsions for therapeutic administration of carotenoids. This review presents a comprehensive update of the therapeutic potential of the carotenoids along with the challenges in achieving an optimized delivery tool for maximizing their effectiveness inside the body.

Purpose: Nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H₂S) are physiologically relevant gaseous neurotransmitters that are endogenously produced in mammalian tissues. In the present study, we investigated the possibility that NO and CO can regulate the endogenous levels of H₂S in bovine isolated neural retina. Methods: Isolated bovine neural retina were homogenized and tissue homogenates were treated with a NO synthase inhibitor, NO donor, heme oxygenase-1 inhibitor, and/donor. H₂S concentrations in bovine retinal homogenates were measured using a well-established colorimetric assay. Results: L-NAME (300 nM–500 μM) caused a concentration-dependent decrease in basal endogenous levels of H₂S by 86.2%. On the other hand, SNP (10–300 μM) elicited a concentration-related increase in H₂S levels from 18.3 nM/mg of protein to 65.7 nM/mg of protein. ZnPP-IX (300 nM–10 μM) caused a concentration-dependent increase in the endogenous production of H₂S whereas hemin (300 nM–20 μM) attenuated the basal levels of H₂S. Conclusion: We conclude that changes in the biosynthesis and availability of both NO and CO can interfere with the pathway/s involved in the production of H₂S in the retina. The demonstrated ability of NO, CO and H₂S to interact in the mammalian retina affirms a physiological/pharmacological role for these gaseous mediators in the eye.

The gaseous signalling molecule, hydrogen sulfide (H₂S) has antioxidant, anti-inflammatory and anti-apoptotic properties. Since oxidative stress has been implicated in the pathogenesis of cataracts and lenticular hydrogen peroxide (H₂O₂) is elevated in some cataract patients, the present study investigated the ability of H₂S-releasing compounds to prevent H₂O₂-induced cataract formation in cultured bovine lenses. Lenses were cultured in either Dulbelcco’s Modified Eagle Medium (DMEM; control); H₂O₂ (50 mM); ascorbic acid (AA; 3 mM) (positive control); and the H₂S-releasing compounds (diallyl trisulfide [DATS] or GYY4137) in the presence of H₂O₂ (50 mM). Lens opacity was determined using a plate reader to measure transmittance. Lens glutathione content (GSH), superoxide dismutase (SOD) activity and lactate dehydrogenase (LDH) cytotoxicity were assessed before and after treatment with the H₂S-releasing compounds. Both DATS (10⁻⁷M - 10⁻⁴M) and GYY4137 (10⁻⁷M - 10⁻⁴M) significantly (p<0.001) attenuated H₂O₂ (50 mM)-induced loss in transmittance, with DATS (10⁻⁴M) and GYY4137 (10⁻⁷M) achieving a maximal reversal of opacity by 56.86±0.01% (n = 6) and 8.39 ± 0.11% (n = 6) after 120 hours, respectively. These observations were corroborated by photographic evaluation, where DATS (10⁻⁵M - 10⁻⁴M) and GYY4137 (10⁻⁷M - 10⁻⁵M)-treated lenses had relatively clear grids after 120 hours, compared to H₂O₂ (50 mM)-treated lenses. The H₂O₂ (50 mM)-induced decline in total GSH content and total SOD activity were significantly (p<0.001; n=5) reversed by DATS (10⁻⁴M) and GYY4137 (10⁻⁷M). After 24 hours, DATS (10⁻⁴M) and GYY4137 (10⁻⁷M) significantly (p<0.001; n=4) reduced cytotoxicity of primary bovine lens epithelial cells by 33.88 ± 4.59% and 36.19 ± 10.53%, respectively. Both H₂S-releasing compounds protected cultured bovine lenses against oxidative stress-induced cataract formation. The slow-releasing H₂S compound, GYY4137 was more potent than DATS in restoring lenticular total GSH content and total SOD activity along with reducing H₂O₂ (50mM)-induced cytotoxicity.

Background: We have evidence that hydrogen sulfide (H₂S)-releasing compounds can reduce intraocular pressure in normotensive and glaucomatous rabbits by increasing the aqueous humor (AH) outflow through the trabecular meshwork. Since H₂S has been reported to possess neuroprotective actions, the prevention of retinal ganglion cell loss is an important strategy in the pharmacotherapy of glaucoma. Consequently, the present study aimed to investigate the neuroprotective actions of H₂S-releasing compounds against hydrogen peroxide (H₂O₂)-induced oxidative stress in an isolated bovine retina. Materials and Methods: The isolated neural retinae were pretreated with a substrate for H₂S biosynthesis called L-cysteine, with the fast H₂S-releasing compound sodium hydrosulfide, and with a mitochondrial-targeting H₂S-releasing compound, AP123, for thirty minutes before a 30-min oxidative insult with H₂O₂ (100 µM). Lipid peroxidation was assessed via an enzyme immunoassay by measuring the stable oxidative stress marker, 8-epi PGF2α (8-isoprostane), levels in the retinal tissues. To determine the role of endogenous H₂S, studies were performed using the following biosynthesis enzyme inhibitors: aminooxyacetic acid (AOAA, 30 µM); a cystathione-β-synthase/cystathionine-γ-lyase (CBS/CSE) inhibitor, α–ketobutyric acid (KBA, 1 mM); and a 3-mercaptopyruvate-s-sulfurtransferase (3-MST) inhibitor, in the absence and presence of H₂S-releasing compounds. Results: Exposure of the isolated retinas to H₂O₂ produced a time-dependent (10–40 min) and concentration-dependent (30–300 µM) increase in the 8-isoprostane levels when compared to the untreated tissues. L-cysteine (10 nM–1 µM) and NaHS (30 –100 µM) significantly (p < 0.001; n = 12) prevented H₂O₂-induced oxidative damage in a concentration-dependent manner. Furthermore, AP123 (100 nM–1 µM) attenuated oxidative H₂O₂ damage resulted in an approximated 60% reduction in 8-isoprostane levels compared to the tissues treated with H₂O₂ alone. While AOAA (30 µM) and KBA (1 mM) did not affect the L-cysteine evoked attenuation of H₂O₂-induced oxidative stress, KBA reversed the antioxidant responses caused by AP123. Conclusions: In conclusion, various forms of H₂S-releasing compounds and the substrate, L-cysteine, can prevent H₂O₂-induced lipid peroxidation in an isolated bovine retina.

Both hydrogen sulfide and endocannabinoids can protect the neural retina from toxic insults under in vitro and in vivo conditions. Purpose: The aim of the present study was two-fold: (a) to examine the neuroprotective action of cannabinoids [methanandamide and 2-arachidonyl glycerol (2-AG)] against hydrogen peroxide (H₂O₂)-induced oxidative damage in the isolated bovine retina and (b) to evaluate the role of endogenously biosynthesized hydrogen sulfide (H₂S) in the inhibitory actions of cannabinoids on the oxidative stress in the bovine retina. Methods: Isolated neural retinas from cows were exposed to oxidative damage using H₂O₂ (100 µM) for 10 min. When used, tissues were pretreated with methanandamide (1 nM–100 nM) and 2-AG (1–10 µM) for 30 min before a 10 min treatment with H₂O₂ (100 µM). In some experiments, retinas were pretreated with inhibitors of the biosynthesis of H₂S [cystathionine β-synthase/cystathionine γ-lyase (CBS/CSE), aminooxyacetic acid, AOAA 30 µM, or 3-mercaptopyruvate sulfurtransferase (3MST), α-keto-butyric acid, KBA 1 mM] and the CB1-receptor antagonist, AM251 (100 nM) for 30 min before treatment with methanandamide (1 nM–100 µM). Enzyme immunoassay measurement of 8-epi PGF2α (8-isoprostane) levels was performed to assess lipid peroxidation in retinal tissues. Results: In the presence of H₂O₂ (100 µM), methanandamide (1 nM–100 µM) and 2-AG (1–10 µM) significantly (p < 0.001) blocked the H₂O₂-induced elevation in 8-isoprostane levels in the isolated bovine retina. In the presence of the CB1 antagonist AM251 (100 nM), the effect of methanandamide (1 nM) on the H₂O₂-induced 8-isoprostane production was significantly (p < 0.001) attenuated. While AOAA (30 µM) had no significant (p > 0.05) effect on the inhibition of H₂O₂-induced oxidative stress elicited by methanandamide, KBA (1 mM) reversed the neuroprotective action of methanandamide. Conclusions: The cannabinoids, methanandamide and 2-AG can prevent H₂O₂-induced oxidative stress in the isolated bovine retina. The neuroprotective actions of cannabinoids are partially dependent upon the activation of the CB1 receptors and endogenous production of H₂S via the 3-MST/CAT pathway.