Reactive Oxygen Species and Eye Aging in Cataracts through Biomolecular Mechanisms

The cataractogenesis process and the novel mechanisms involved in its progression make us question that the only solution today presented for its resolution is through a surgical procedure. The unveiling of such interesting and intricate machinery in the lens opacification occupies not only the ophthalmologists field, but also biology, molecular, and biochemistry areas. The animal models, experimental and theoretically, have done their best try to present what appears to be an irreparable and unstoppable process nowadays. The crystalline lens opacification is chronic and progressively damaged due to the loss of balance between the production and elimination of free reactive oxygen species (ROS), the attempts to stop or slow down this overproduction or lack of elimination lie in study material from disciplines as complex as cancer pathways. The execution of this review article was possible through metasearch engines like Wiley Online Library, EBSCO, Cochrane, Clinical key and MEDLINE PubMed (National Library of Medicine, National Institutes of Health), to retrieve studies from January 2021 to January 2022, following PRISMA guidelines, with a special affinity to systematic reviews and meta-analysis. MeSH Terms associated with "Cataract AND Reactive Oxygen Species". This work constitutes an integral cataractogenesis view in the development of future therapeutic scopes. The world population especially in Europe is aging at a rapid rate, in this sense is necessary to consider a root potential solution and not palliative strategies in ophthalmology for the next generations. The compendium of procedures presented already supposed to open a new panorama to a clearer world, a world without senile cataracts. Time is vision.

The Effect of Pinitol on Cataractogenesis and Anti-oxidative effect in Streptozotocin Induced Diabetic Rats

PURPOSE: Pinitol, a natural extract of soybeans, is metabolized to chiroinositol in the body. We evaluated the ability of pinitol to protect diabetic cataracts from oxidative stress in streptozotocin (STZ)-induced diabetic rats. METHODS: We used Sprague-Dawley rats (n=80). Diabetes was induced with STZ (60 mg/kg, i.p.). These STZ-injected rats were administered pinitol or chiroinositol, each 20 mg/ml, and given access to regular chow. The efficacies of pinitol and chiroinositol were studied by monitoring a series of lens opacity and corneal lesion by photodocumentation. Aqueous humor and lens samples were collected at the 2nd week, 4th week, and 12th week. We measured glutathione, malondialdehyde (MDA) and used ELISA to evaluate its antioxidant effect. RESULTS: STZ-diabetic rats showed typical Y sutural lens opacity beginning on the 3rd day and progressed diffusely to more cortical opacity from the 1st week. However, in pinitol-treated diabetic rats, these cataractous changes were remarkably decreased. Corneal edema and opacity also remarkably reduced in the pinitol-treated group. Glutathione level markedly increased compared to that of the non-treated diabetic group (230.12+/-10.96 micrometer, 156.42+/-5.09 micrometer, respectively). This resulted in a decrease in peroxidized MDA product in the treated group. Similarly, the anti-cataractogenic and anti-oxidative effects of pinitol were also observed in the chiroinositol-treated group. CONCLUSIONS: These results suggest that pinitol could be effective in preventing cataract and cornea edema caused by oxidative stress in a hyperglycemic environment.

Transdifferentiation of Cultured Bovine Lens Epithelial Cells into Myofibroblast-like Cells by Serum Modulation

An after-cataract is caused by the proliferation of residual cells over the equator of the lens. These cells subsequently migrate to the posterior lens capsule, where they undergo aberrant differentiation into fiber-like cells or transdifferentiation into fibroblast-like cells. To study the precise molecular mechanisms of transdifferentiation, an attempt was made to establish an in vitro system, in which the lens epithelial cells (LECs) of the pre-equatorial zone could be transdifferentiated into fibroblast-like cells. The required conditions for culturing the LECs were identified as consisting of four phases; intact bovine explants, explant-cultured, serum-modulated and additionally modulated LECs. The LECs of each phase were compared by examining changes in the expression of the epithelial-mesenchymal transition (EMT) -related genes and changes in cellular morphology and adhesion. The explants that were cultured in a medium containing 10% fetal bovine serum (FBS) for 2 weeks, showed changes in the expression of the EMT-related genes, although the other explant-cultured cells maintained an epithelial morphology. To introduce a transition into mesenchymal cells, the explant cultures were subcultured in a medium containing 20% FBS for six passages. These cells displayed an elongated morphology and were able to grow and migrate in a similar way to fibroblast cells. The expression of the EMT-related genes, such as, extracellular matrix proteins and integrins, was altered. This was similar to the alteration of the 3-dimensional collagen gels model previously reported. During a further process of EMT by additional serum modulation, the inhibitory effect of disintegrin on cell adhesion was gradually decreased, integrin expression was differentially regulated and alpha-smooth muscle actin was post-translationally modified from the point of passage number six. Overall, it can be concluded that terminal transdifferentiation accompanies changes in the cytoskeletal proteins and cell surface molecules. These are modulated in systematic patterns of post-transcriptional and post-translational regulation and patterns of gene regulation, by the synergic effects of several transforming factors contained in serum. Therefore, posterior capsular opacification may also be accompanied by this molecular mechanism.

Possible Role of Amyloid beta- (1-40) -BSA Conjugates in Transdifferentiation of Lens Epithelial Cells

We investigated whether amyloid beta (Abeta) aggregates have transforming growth factor beta- like cytokine activity and cause transdifferention of lens epithelial cells, leading to certain types of cataract. In order to mimic Abetaaggregates, Abeta- (1-40) was crosslinked to bovine serum albumin (BSA) with disuccinimidyl suberate according to a previously described procedure. When human lens epithelial B-3 (HLE B-3) cells were treated with the Abeta- (1-40) -BSA conjugates, we observed the translocation of Smad-3, as well as the induced mRNA levels of fibronectin (FN), collagen type I (Col I), smooth muscle actin (SMA) and matrix metalloproteinase-2 (MMP-2). In addition, we investigated the morphology of rat whole lens cultured for 5 days in the presence of Abeta- (1-40) -BSA, and the immunohistochemical localizations of Abeta- (1-40) /amyloid precursor protein (APP) in human clinical tissues beneath the anterior capsules. In rat whole lens cultures, treatment with Abeta- (1-40) -BSA produced a transformed morphology that had multiple layers of lens epithelial cells. To compare the anterior capsules in anterior subcapsular cataracts with those in nuclear cataracts, immunohistochemical studies of Abeta/APP in human clinical tissues revealed that the predominant immunostaining of Abeta occurs in the anterior epithelial plaques, which likely produces the abnormal extracellular matrix. Thus, these findings suggest that Abeta aggregates in vivo are possibly involved in the regulatory process by which lens epithelial cells may transdifferentiate into fibroblast-like cells, as well as help understand the mechanisms which lead to certain types of cataractogenesis.

The Role of Nitric Oxide in the Cataract Development: A Possible Mechanism of Lens Opacity

PURPOSE: To assess the role of nitric oxide in the development of cataract by detection of nitrotyrosine, which is a reaction product of peroxynitrite with tyrosine. METHODS: We have collected aqueous humor and anterior capsule of lens after cataract surgery from 14 eyes. We classified lens opacities into three types such as nuclear sclerosis, cortical and posterior subcapsular opacity. Nitrite, stable oxidative product of nitric oxide, was measured in the aqueous humor and immunohistochemical staining for nitrotyrosine was performed to examine anterior capsules. RESULTS: The concentrations of nitric oxide in aqueous humor were 0.0698+/-0.0036, 0.0652+/-0.0116, and 0.0700+/-0.0022 mM in nuclear sclerosis, cortical and posterior subcapsular opacity, respectively and no significant differences existed among lens opacity types. In lenses with cortical and posterior subcapsular opacity, the expression of nitrotyrosine was observed around epithelial cell and intercellular space. There was no expression of nitrotyrosine in lenses with nuclear sclerosis. CONCLUSIONS: This results suggest that nitration of tyrosine by peroxynitrite is possibly related to the cataractogenesis of lenses with cortical and posterior subcapsular opacity.

The Role of Nitric Oxide on Cataractogenesis in Uveitis Model Induced by Concanavalin A and Lipopolysaccharide

Nitric oxide[NO]plays a diverse role in many biological systems such as vascular, nervous and respiratory system. Recently, many studies have been performed to define the relationship between NO and physiological and pathophysiological processes. This study was conducted to evaluate the role of NO on cataractogenesis in uveitis model induced by Con A and LPS. Forty-five white male rabbits were divided into five experimental groups[ten rabbits for each group I, II, III, IV;five rabbits for group V, control]. The rabbits were received intravitreal injection of Con A[I], Con A &L-NAME [II], LPS[III], LPS &L-NAME[IV], BSS[Vfor control], respectively. After injection, the author evaluated the inflammatory grade, cataractous lens changes, NO[nitrite+nitrate]concentration in response to each material in aqueous humor and vitreous cavity and MDA concentration of lens with time interval. Other 7 rabbits 'eyes were enucleated and 14 fresh lenses were extracted to investigate the correlation with in vivo study via lens culture in 12-well plate. These results suggested that NO was closely related to Con A and LPS induced cataractogenesis in uveitis model and Con A was a more reliable candidate due to its prolonged effect. NOS inhibitors could suppress both inflammation and cataract formation. Potent oxidant, peroxynitrite played an important role on NO related cataractogenesis. So, on the clinical basis, NOS inhibitors may be useful in prevention of cataract in inflammatory condition of the eyes but further studies are needed for the confirmation of stability and selectivity of the NOS inhibitors.

The Role of Nitric Oxide on Cataractogenesis in Uveitis Model Induced by Concanavalin A and Lipopolysaccharide

Nitric oxide[NO]plays a diverse role in many biological systems such as vascular, nervous and respiratory system. Recently, many studies have been performed to define the relationship between NO and physiological and pathophysiological processes. This study was conducted to evaluate the role of NO on cataractogenesis in uveitis model induced by Con A and LPS. Forty-five white male rabbits were divided into five experimental groups[ten rabbits for each group I, II, III, IV;five rabbits for group V, control]. The rabbits were received intravitreal injection of Con A[I], Con A &L-NAME [II], LPS[III], LPS &L-NAME[IV], BSS[Vfor control], respectively. After injection, the author evaluated the inflammatory grade, cataractous lens changes, NO[nitrite+nitrate]concentration in response to each material in aqueous humor and vitreous cavity and MDA concentration of lens with time interval. Other 7 rabbits 'eyes were enucleated and 14 fresh lenses were extracted to investigate the correlation with in vivo study via lens culture in 12-well plate. These results suggested that NO was closely related to Con A and LPS induced cataractogenesis in uveitis model and Con A was a more reliable candidate due to its prolonged effect. NOS inhibitors could suppress both inflammation and cataract formation. Potent oxidant, peroxynitrite played an important role on NO related cataractogenesis. So, on the clinical basis, NOS inhibitors may be useful in prevention of cataract in inflammatory condition of the eyes but further studies are needed for the confirmation of stability and selectivity of the NOS inhibitors.

Population based Study of Risk Factors and Environmental Factors Contributing to Cataractogenesis

To evaluate the prevalence and related risk factors of the senile cataract, we performed epidemiologic study in two different geographic area with population based study in the group of 40 years or more old subjects. The results of this study are as follow. The prevalence rate of senile cataract was 32.8% in mountainous area (Chung Won) and 43.3% in rural area (Mun Kyung). The prevalence rate in both area had strong tendency to increase according to age, especially after 7th decade. But there was no clear relationship between male and female. In geographic characterisitic, annual sunshine time was longer, but cloud cover was lesser in Mun Kyung. Also related risk factors of senile cataract were smoking, low education level and poor health status. The cataract was more common in patients with diabetes, hypertension and arthritis. And long term use of steroids, antihypertensive drugs and analgesics for arthritis were risk factors for the cataractogenesis. But alchol consumption and number of pregnacny were not contributing to cataractogenesis. As a result, the senile cataract has mulifactorial factors and its process is complex phenomenon which is still partially known.