Progression Of Age-related Cataract Research Articles

Astaxanthin ameliorates oxidative stress in lens epithelial cells by regulating GPX4 and ferroptosis

Ferroptosis is a form of regulated cell death closely associated with oxidative stress and mitochondrial dysfunction and is characterised by the accumulation of reactive oxygen species (ROS) and lipid species and iron overload. Damage to human lens epithelial cells (LECs) is associated with age-related cataract progression. Astaxanthin (ATX), a carotenoid with natural antioxidant properties, counteracts ferroptosis in the treatment of various degenerative diseases. However, this mechanism has not been reported with respect to cataract treatment. In this study, the differential expression levels of glutathione peroxidase 4 (GPX4) in the lens of young and aged mice were analysed. Continuous ATX supplementation for 8 months upregulated GPX4 expression in the mouse LECs and delayed the progression of ferroptosis. Upon treatment with erastin, ROS and malondialdehyde accumulated and the mitochondrial membrane potential decreased. At the same time, the expressions of GPX4, SLC7A11, and ferritin were suppressed in human LECs. All of these phenomena were partially reversed by ATX and Fer-1, a ferroptosis inhibitor. This study confirmed that the ATX-mediated targeting of GPX4 might alleviate human LECs damage by inhibiting ferroptosis and ameliorating oxidative stress and that this could represent a promising therapeutic approach for age-related cataract.

Antioxidant and free radicals species in the aqueous humor of patients with age-related cataract

Introduction/Objective. Age-related cataract is a significant cause of visual impairment worldwide. Oxidative damage and the effects of free radical species are considered important in the etiopathogenesis of cataracts. The aim of this study was to evaluate the antioxidative capacity and oxidative stress in the aqueous humor (AH) according to age and cataracts maturity. Methods. Clinical and biochemical researches were carried out in 55 patients with age-related cataract. According to the cataract maturity, patients were classified into incipient (cortical ? group C, 18 patients; nuclear ? group N, 20 patients; mature ? group M, 17 patients). In order to evaluate the impact of age patients within each group were divided into Group I (65?69 years) and Group II (70 ? years). The antioxidant activity of AH was measured by the reduction power method and the activity of glutathione peroxidase (GPx) spectrophotometrically. Changes in the concentrations of hydroxyl and ascorbyl radicals were detected by electron spin resonance spectroscopy. Results. Both reduction power and GPx activity were significantly (p < 0.001) reduced in group N compared to group C and in group M compared to group N. Concentrations of hydroxyl (29.45 ? 1.01% in group C, 38.12 ? 1.29% in group N, and 74.14 ? 2.52% in group M) and ascorbyl radicals (26.12 ? 0.89% in group C, 41.15 ? 1.39% in group N, and 83.56 ? 2.84% in group M) increased significantly (p < 0.05) with progression of age-related cataract. Significant negative correlation (r = -0.759, p < 0.05) was determined between concentrations of HO? and content of GPx. Conclusion. Our research proved that the level of oxidative stress in the AH is significantly affected during aging and cataract progression, The obtained data support the hypothesis that during aging, depending on the maturity of the cataract, the antioxidant capacity in the AH decreases due to an increase in the concentration of reactive HO?.

Incidence, progression and risk factors of age-related cataract in Malays: The Singapore Malay Eye Study.

Long-term data on age-related cataract, a leading cause of blindness and visual impairment, is scarce in Asian populations. We report the 6-year incidence and progression of age-related cataract and associated risk factors in Malay adults living in Singapore. Population-based cohort study. A total of 3280 Malays aged 40+ years participated in baseline examinations of the Singapore Malay Eye Study (2004-2006). Six years later, 1901 (72.1% of eligible) baseline participants were re-examined. Cataract was assessed using lens photos, taken during eye examinations, following the Wisconsin Cataract Grading System. Incidence and progression of cortical, nuclear and posterior subcapsular (PSC) cataract. Poisson regression models and generalized estimating equations models (with Poisson link) were used to assess factors associated with cataract incidence and progression, respectively, adjusting for age, sex and other risk factors. Age-adjusted 6-year incidence of cortical, nuclear and PSC cataract was 14.1%, 13.6% and 8.7%, respectively, and was strongly age-related (P for trend <.001 for all types). Diabetes (relative risk [RR], 1.97; 95% confidence intervals [CI], 1.46-2.67) was associated with incident cortical cataract, hypertension was associated with PSC cataract incidence (RR, 2.09; 95% CI, 1.22-3.61), after multivariable adjustment. Progression occurred in 20.4%, 5.9% and 40.6% of baseline cortical, nuclear and PSC cataract cases, respectively. Similar to other elderly populations, incidence and progression of cataract were common in this Malay population. Diabetes and hypertension were important modifiable risk factors for cataract, highlighting the importance of systemic health on eye disease.

LncRNA PLCD3-OT1 Functions as a CeRNA to Prevent Age-Related Cataract by Sponging miR-224-5p and Regulating PLCD3 Expression.

Long noncoding RNAs (lncRNAs) are important in disease progression and cellular functions. This study aimed to conduct global lncRNA profiling and characterize the role of lncRNA 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase delta 3-sence RNA 1 (PLCD3-OT1) in the progression of age-related cataract (ARC). We performed lncRNA expression profiling of lens capsule from ARC groups and age-matched groups using high-throughput RNA-sequencing. Real-time PCR was conducted to detect the expression pattern of lncRNA and mRNA in the clinical samples and cell model. Assays of cell-counting kit-8, 5'-ethynyl-2'-deoxyuridine, TUNEL, and propidium iodide staining were used to detect cell viability, proliferation, apoptosis, and cell cycle. We also performed fluorescence in situ hybridization assay to detect the location of lncRNA, and verified the endogenous competitive RNA mechanism between miRNAs, lncRNAs, and target genes via double-luciferase reporter analyses. The expression of lncRNA PLCD3-OT1 and PLCD3 were significantly decreased in ARC. PLCD3-OT1 overexpression promoted the expression of PLCD3, cell viability, proliferation, and inhibited cell apoptosis upon oxidative stress, while knockdown of PLCD3 showed the opposite results. Mechanistically, PLCD3-OT1functions through positively regulation the expression of PLCD3. In addition, PLCD3-OT1 may act as a ceRNA to regulate the expression of PLCD3 through competition for miR-224-5p. PLCD3-OT1 and PLCD3 may become potential therapeutic targets for the prognosis, diagnosis, and treatment of ARC.

Grape seed extract and zinc containing nutritional food supplement prevents onset and progression of age-related cataract in wistar rats.

To study possible inhibition of oxidative stress and cataract formation by single combined formulation of grape seed extract and Zincovit tablets against sodium selenite-induced age-related cataract in Wistar rat pups. Oxidative stress and consequent cataract formation was induced by subcutaneous administration of a single dose of sodium selenite (10 µmoles/kg) to Wistar rat pups on day 7 post-natally. In experiments designed to inhibit such cataract formation, the pups were pretreated subcutaneously with combined formulation of grape seed extract and Zincovit tablets (40, 80 and 160 mg/kg), one day prior to the administration of selenite and continuing such treatment till day 20, when the experiments were terminated. The extent of tissue damage caused by the selenite was assessed biochemically by measurements of the levels of reduced glutathione, glutathione peroxidase, glucose-6-phosphate dehydrogenase, protein thiol, catalase, superoxide dismutase, malondialdehyde, aldose reductase, sorbitol dehydrogenase and adenosine triphosphate in the isolated lenses. Cataract formation and its prevention were monitored by examining the eye with pen light illumination and subsequent photography of the isolated lenses. Injection of selenite led to a significant loss of lens clarity due to cataract formation. In the group treated with combined formulation of grape seed extract and Zincovit tablets, the formation of cataract was significantly prevented. In the normal and selenite induced senile cataract control group, the levels of lens oxidative stress markers, G6PD and ATP were substantially lower than in the grape seed extract with Zincovit tablets treated group (p < 0.05). Over all, the results suggest that single combined formulation of grape seed extract and Zincovit tablets may offer a prophylactic measure against onset and progression of age- related cataract of human subjects as nutritional food supplement.

Resveratrol Delays Age-Related Deterioration and Mimics Transcriptional Aspects of Dietary Restriction without Extending Life Span

A small molecule that safely mimics the ability of dietary restriction (DR) to delay age-related diseases in laboratory animals is greatly sought after. We and others have shown that resveratrol mimics effects of DR in lower organisms. In mice, we find that resveratrol induces gene expression patterns in multiple tissues that parallel those induced by DR and every-other-day feeding. Moreover, resveratrol-fed elderly mice show a marked reduction in signs of aging, including reduced albuminuria, decreased inflammation, and apoptosis in the vascular endothelium, increased aortic elasticity, greater motor coordination, reduced cataract formation, and preserved bone mineral density. However, mice fed a standard diet did not live longer when treated with resveratrol beginning at 12 months of age. Our findings indicate that resveratrol treatment has a range of beneficial effects in mice but does not increase the longevity of ad libitum-fed animals when started midlife.

Centrum Use and Progression of Age-Related Cataract in the Age-Related Eye Disease Study: A Propensity Score Approach. AREDS Report No. 21

To evaluate the effect of the multivitamin Centrum on the development and progression of age-related lens opacities. Clinic-based prospective cohort study. Four thousand five hundred ninety individuals with at least one natural lens and photographic follow-up (median, 6.3 years) were assessed for development or progression of lens opacities. Progression of "any" lens opacity or type-specific opacity was ascertained from lens photographs taken at baseline and at annual visits beginning at year 2. The Age-Related Eye Disease Study (AREDS) showed no statistically significant effect of a high-dose antioxidant formulation on progression of lens opacities. Centrum also was provided to approximately two thirds of the study participants. Because Centrum use was elective, a logistic regression model of baseline characteristics was used to generate a propensity score for Centrum use. Repeated-measures logistic regression, adjusted for propensity score and other covariates, was used to evaluate associations of Centrum use and lens opacity. Centrum use, adjusted for propensity score and other covariates, was associated with a reduction in "any" lens opacity progression (odds ratio [OR] = 0.84, 95% confidence interval [CI] = 0.72-0.98, P = 0.025). Results for individual lens opacity types suggested that Centrum use was protective for nuclear opacity events (OR = 0.75, 95% CI = 0.61-0.91, P = 0.004). Observational data from the AREDS and other studies suggest that use of a multivitamin may delay the progression of lens opacities. A National Eye Institute-sponsored clinical trial scheduled for completion in 2007 will provide additional data on Centrum use and cataract development.

Age-related cataract progression in five mouse models for anti-oxidant protection or hormonal influence

Five mouse models with known alterations of resistance to oxidative damage were compared by slit lamp examination for the presence and degree of advancement of age-related cataract in young adult and old animals along with wild type controls. A group of young and old normal C57BL/6Jax mice were examined first to constitute a standard, and they were found to exhibit age-related cataract development. Following this, four models on the C57BL/6 background with imposed genetic alterations affecting anti-oxidant enzyme presence or activity, and one outbred model in which a deletion blocked the growth hormone/IGF-1 axis, were similarly examined. There was no evidence of foetal or juvenile cataract development in any of these models, and an age-related severity for lens opacities was shown between young adult and old mice in all groups. Model 1, mice null for the anti-oxidant gene glutathione peroxidase-1 (GPX1) had significantly advanced cataracts in older mice vs. same age controls. In mouse model 2 hemizygous knockout of SOD2 (MnSOD) did not affect age-related cataract development. In model 3 combining the GPX1 and SOD2 deficiencies in the same animal did not advance cataract development beyond that of the GPX1 null alone. In model 4 the addition of anti-oxidant protection in the lens by transfection of human catalase targeted only to the mitochondria resulted in a significant delay in cataract development. The 5th model, growth hormone receptor knockout ( GHR−/−) mice, also demonstrated a significant reduction in age-related cataract development, as well as dwarfism. These findings, in general, support the oxidative theory of age-related cataract development. The exception, the partial deletion of SOD2 in the hemizygous KO model, probably did not represent a sufficiently severe deprivation of anti-oxidant protection to produce pathologic changes in the lens.

VITAMIN E SUPPLEMENTATION AND CATARACT

Abstract Objective To determine whether treatment with vitamin E (500 IU daily) reduces either the incidence or rate of progression of age-related cataracts. Design A prospective, randomized, double-masked, placebo-controlled clinical trial entitled the Vitamin E, Cataract and Age-Related Maculopathy Trial. Participants Of 1906 screened volunteers, 1193 eligible subjects with early or no cataract, aged 55 to 80 years, were enrolled and followed up for 4 years. Intervention Subjects were assigned randomly to receive either 500 IU of natural vitamin E in soybean oil encapsulated in gelatin or a placebo with an identical appearance. Main outcome measures The incidence and progression rates of age-related cataract were assessed annually with both clinical lens opacity gradings and computerized analysis of Scheimpflug and retroillumination digital lens images obtained with a Nidek EAS-1000 lens camera. The analysis was undertaken using data from the eye with the more advanced opacity for each type of cataract separately and for any cataract changes in each individual. Results Overall, 87% of the study population completed the 4 years of follow-up, with 74% of the vitamin E group and 76% of the placebo group continuing on their randomized treatment allocation throughout this time. For cortical cataract, the 4-year cumulative incidence rate was 4.5% among those randomized to vitamin E and 4.8% among those randomized to placebo ( P = 0.87). For nuclear cataract, the corresponding rates were 12.9% and 12.1% ( P = 0.77). For posterior subcapsular cataract, the rates were 1.7% and 3.5% ( P = 0.08), whereas for any of these forms of cataract, they were 17.1% and 16.7%, respectively. Progression of cortical cataract was seen in 16.7% of the vitamin E group and 18.4% of the placebo group ( P = 0.76). Corresponding rates for nuclear cataract were 11.4% and 11.9% ( P = 0.84), whereas those of any cataract were 16.5% and 16.7%, respectively. There was no difference in the rate of cataract extraction between the 2 groups ( P = 0.87). Lens characteristics of the participants withdrawn from the randomized medications were not different from those who continued. Conclusions Vitamin E given for 4 years at a dose of 500 IU daily did not reduce the incidence of or progression of nuclear, cortical, or posterior subcapsular cataracts. These findings do not support the use of vitamin E to prevent the development or to slow the progression of age-related cataracts.