Status of oxidative stress markers, advanced glycation index, and polyol pathway in age-related cataract subjects with and without diabetes.

One of the major public health issues is the rising prevalence of cataracts, a primary reason for preventable blindness. The causes for the development of age-related cataracts and accelerated cataractogenesis in diabetes are multifactorial. Hence, this study was designed to examine the status and relationship between the three majorly associated molecular events, namely, oxidative stress, non-enzymatic glycation, and polyol pathway in age-related cataracts with and without diabetes. A total of 472 subjects were distributed into four groups: non-diabetic subjects with clear lens (135), diabetic subjects with clear lens (40), non-diabetic subjects with cataract (174), and diabetic subjects with cataract (123). Cataracts were graded by slit-lamp examination according to the Lens Opacities Classification System III. Age at onset of cataract, type of opacity, anthropometric measurements, and sociodemographic characteristics were recorded, and clinical profile was examined. Plasma oxidative stress markers were assessed by estimating the lipid peroxidation end product malondialdehyde, protein oxidation products protein carbonyls, and DNA oxidative damage marker 8-hydroxy-2-deoxyguanosine. Plasma advanced glycation end products index, erythrocyte aldose reductase activity, and sorbitol levels were evaluated. After adjusting for age, plasma malondialdehyde levels were significantly higher in diabetic cataracts (P < 0.001) and non-diabetic cataract subjects (P < 0.05), compared to non-diabetic subjects with clear lens. Plasma advanced glycation end products index was significantly higher (P < 0.05) only in diabetic cataracts, but not in non-diabetic subjects with cataracts. Aldose reductase activity and sorbitol levels were significantly higher (P < 0.001) in both diabetic and non-diabetic subjects with cataract compared to non-diabetic subjects with clear lens. The data indicated that plasma lipid peroxidation in age-related cataracts was independent of diabetes. An association of pronounced glycation was observed only in diabetic cataracts but not in non-diabetic cataracts and polyol flux between diabetic cataracts and non-diabetic cataracts was comparable.

Wholegrain and legume consumption and the 5-year incidence of age-related cataract in the Blue Mountains Eye Study.

The present study aims to investigate the effect of wholegrain and legume consumption on the incidence of age-related cataract in an older Australian population-based cohort. The Blue Mountains Eye Study (BMES) is a population-based cohort study of eye diseases among older adults aged 49 years or older (1992-1994, n 3654). Of 2334 participants of the second examination of the BMES (BMES 2, 1997-2000), 1541 (78·3 % of survivors) were examined 5 years later (BMES 3) who had wholegrain and legume consumption estimated from the FFQ at BMES 2. Cataract was assessed using photographs taken during examinations following the Wisconsin cataract grading system. Multivariable-adjusted logistic regression models were used to assess associations with the 5-year incidence of cataract from BMES 2 (baseline) to BMES 3. The 5-year incidence of cortical, nuclear and posterior subcapsular (PSC) cataract was 18·2, 16·5 and 5·9 %, respectively. After adjustment for age, sex and other factors, total wholegrain consumption at baseline was not associated with incidence of any type of cataract. High consumption of legumes showed a protective association for incident PSC cataract (5th quintile: adjusted OR 0·37; 95 % CI 0·15, 0·92). There was no significant trend of this association across quintiles (P = 0·08). In this older Australian population, we found no associations between wholegrain intake at baseline and the 5-year incidence of three cataract types. However, intake of legumes in the highest quintile, compared with the lowest quintile, may protect against PSC formation, a finding needing replication in other studies.

Resveratrol delay the cataract formation against naphthalene-induced experimental cataract in the albino rats.

Oxidative stress-induced toxicity plays a major role in ocular diseases such as retinal degeneration, age-related cataract (ARC) formation and macular dystrophy. In this study, we explored the possible role of resveratrol (RSV) at the different dose levels (10, 20 and 40 mg/kg/day, ip) in an experimental model of naphthalene (1 g/kg/day, po)-induced age-related cataracts. Morphological changes in the eyes of the rats in two groups, the RSV and the ARC groups, were monitored weekly, and biochemical parameters in the lenses were assessed after completion of the experimental work. A comparison between the rats in the two groups showed that treatments at RSV doses of 20 and 40 mg/kg/day significantly retarded lenticular opacity, restored antioxidants (CAT, SOD, GPX, GSH), Ca2+ ATPase function, and protein contents, and reduced lipid peroxidation in the lenses of the animals in the RSV group. The treatment with resveratrol at a dose of 10 mg/kg/day did not show any anti-cataractogenic effects. Based on the results of our investigation, we conclude that supplemental doses of resveratrol at 40 mg/kg/day effectively prevent cataract formation associated with the aging via increased soluble protein contents and Ca2+ homeostasis, apart from the antioxidant restoration. The results demonstrate that RSV treatment may be considered as a promising preventive or supplemental measure for delaying and/or preventing the formation of ARCs.

Preliminary study on whole genome methylation and transcriptomics in age-related cataracts.

DNA methylation plays an important role in the occurrence and development of age-related cataracts (ARC). This study aims to reveal potential epigenetic biomarkers of ARC by detecting modifications to the DNA methylation patterns of genes shown to be related to ARC by transcriptomics. The MethylationEPIC BeadChip (850 K) was used to analyze the DNA methylation levels in ARC patients and unaffected controls, and the Pearson correlation test was used to perform genome-wide integration analysis of DNA methylation and transcriptome data. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to perform functional analysis of the whole genome, promoter regions (TSS1500/TSS200), and the associated differentially methylated genes (DMG). Pyrosequencing was used to verify the methylation levels of the selected genes. The results showed that, compared with the control group, a total of 52,705 differentially methylated sites were detected in the ARC group, of which 13,858 were hypermethylated and 38,847 were hypomethylated. GO and KEGG analyses identified functions related to the cell membrane, the calcium signaling pathway, and their possible molecular mechanisms. Then, 57 DMGs with negative promoter methylation correlations were screened by association analysis. Pyrosequencing verified that the ARC group had higher methylation levels of C3 and CCKAR and lower methylation levels of NLRP3, LEFTY1, and GPR35 compared with the control group. In summary, our study reveals the whole-genome DNA methylation patterns and gene expression profiles in ARC, and the molecular markers of methylation identified herein may aid in the prevention, diagnosis, treatment, and prognosis of ARC.

Characterization of mechanical stress in the occurrence of cortical opacification in age-related cataracts using three-dimensional finite element model of the human lens and RNA-seq.

Cataract is the leading cause of blindness across the world. Age-related cataract (ARC) is the most common type of cataract, but its pathogenesis is not fully understood. Using three-dimensional finite element modeling combining experimental biotechnology, our study demonstrates that external forces during accommodation cause mechanical stress predominantly in lens cortex, basically matching the localization of opacities in cortical ARCs. We identified the cellular senescence and upregulation of PIEZO1 mRNA in HLECs under mechanical stretch. This mechano-induced senescence in HLECs might be mediated by PIEZO1-related pathways, portraying a potential biomechanical cause of cortical ARCs. Our study updates the fundamental insight towards cataractogenesis, paving the way for further exploration of ARCs pathogenesis and nonsurgical treatment.

A lipidomic study on the lens epithelial cells of patients with age related cataracts.

Age related cataracts (ARC) represent the main reason for blindness globally. The lens epithelial cells (LECs) participate not only in the metabolism of many substances in the lens but also in maintaining lens transparency. This study used lipidomics to investigate the metabolic differences in LECs of ARC patients with different severity, aiming at identifying potential metabolic biomarkers of ARC. Patients diagnosed with ARC and underwent cataract surgery at Shanghai Tongren Hospital were selected to participate in this study, which were classified as mild ARC group and severe ARC group. During their cataract surgery, anterior lens capsules(LCs) containing LECs were obtained. The lipidomics of LECs were analyzed using the liquid chromatography­mass spectrometry (LC-MS). Potential pathways of lipids were searched for using databases such as the Kyoto Encyclopedia of Genes and Genomes (KEGG) and MetaboAnalyst platform. In LEC lipids, 26 lipids have been identified as potential biomarkers between mild ARC and severe ARC, with AUC values of 0.67-0.94. The pathway analysis results revealed that the Glycerophospholipid (GPL) metabolism was significantly influenced, indicating that these metabolic markers contribute significantly to regulating this pathway. The LEC metabolic spectrum demonstrates a proficient ability to differentiate between patients with varying levels of cataracts. Herein, we have successfully identified potential metabolic biomarkers and pathways that have proven to be valuable in enhancing our understanding of ARC pathogenesis. The finding has translational value for developing new cataract treatment methods in the future.

A longitudinal analysis of factors associated with age-related cataract among older Australian women: a cohort study of 7851 older Australian women 79-90 years.

BACKGROUND: Age-related cataracts are a significant global health issue due to population ageing. More than 70% of older Australians aged 80 or above have clinically significant age-related cataracts. AIM: The study aimed to identify factors associated with age-related cataracts among older Australian women 79-90 years. METHOD: A 6-year longitudinal analysis of the Australian Longitudinal Study on Women's Health (ALSWH) was conducted on 7117 women from surveys four to six. The women were asked whether they had been diagnosed or treated for cataracts 3 years before each survey. We used generalised estimating equation (GEE) modelling to identify factors independently associated with age-related cataracts. RESULTS: At baseline (79-84 years), 44.8% lived in metropolitan Australia, 67.9% had good general health, 26.5% had private health insurance, 30.6% had cataracts, 28.8% had undergone cataract surgery, 12.0% had diabetes, 24.9% had skin cancer, 56.2% had hypertension, 24.0% had a history of falls, 63.0% had visited general practitioner (GP) frequently, and 48.8% were driving themselves as their main means of transport. In the final model, poor general health [adjusted odds ratio (AOR) = 1.23, 95% CI = 1.14, 1.33)], not driving (AOR = 1.09, 95% CI = 1.01, 1.18), having private health insurance (AOR = 1.13, 95% CI = 1.04, 1.23), frequent GP visits (AOR = 1.16, 95% CI = 1.07, 1.25), skin cancer (AOR = 1.26, 95% CI = 1.16, 1.37), hypertension (AOR = 1.13, 95% CI = 1.05, 1.21), and fall (AOR = 1.12, 95% CI = 1.04, 1.22) were significantly associated with the age-related cataracts. CONCLUSIONS: Systemic diseases, poor quality of life, driving cessation, and health service use were significantly associated with age-related cataracts in older women.

Aberrant expression of COL4A1 in age-related cataract and its effect on cell proliferation, apoptosis and gene expression changes.

AIM: To evaluate the regulation of the aberrant expression of collagen type IV alpha 1 chain (COL4A1) in the development of age-related cataract (ARC). METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot analysis were employed to evaluate the expression of COL4A1 in ARC patients and healthy controls. The proliferation, apoptosis, cell cycle and epithelial-mesenchymal transition (EMT) of human lens epithelial cell (HLE-B3) were further analyzed under the condition of COL4A1 gene silence. Alteration of gene expression at mRNA level after knockdown COL4A1 were also evaluated by qRT-PCR on HLE-B3 cells. RESULTS: The aberrant expression of COL4A1 was identified a clinically associated with the ARC. Silencing of COL4A1 promoted the apoptosis and inhibited the proliferation of HLE-B3 by blocking the cell cycle. Moreover, COL4A1 gene silence didn't affect the cytoskeleton of HLE-B3 but down-regulated the Collagen type IV Alpha 2 Chain (COL4A2), paired box 6 (PAX6), procollagen-lysine 2-oxoglutarate 5-dioxygenases 1 (PLOD1) and procollagen-lysine 2-oxoglutarate 5-dioxygenases 2 (PLOD2) expression levels in HLE-B3 cells. Silencing the COL4A1 gene induced EMT of the HLE-B3 cells by promoting the transforming growth factor beta (TGF-ß) expression. CONCLUSION: Silencing of COL4A1 induces S-phase arrest, also inhibits the proliferation and enhance HLE-B3 apoptosis and EMT, and down-regulates the expression of COL4A2, PAX6, PLOD1 and PLOD2. Thus, the expression alteration of COL4A1 may play a critical role in the pathogenesis of ARC.

Postponement of the opacification of lentoid bodies derived from human induced pluripotent stem cells after lanosterol treatment-the first use of the lens aging model in vitro in cataract drug screening.

Purpose: Our previous study observed that human induced pluripotent stem cell (HiPSC)-derived lentoid bodies (LBs) became cloudy with extended culture time, partially mimicking the progress of human age-related cataracts (ARCs) in a dish. In the present study, lanosterol, a potential anticataract drug, was used to further verify the value of this model in drug screening for cataract treatment. Methods: Mature LBs on day 25, which were differentiated from HiPSCs using the "fried egg" method, were continually cultured and treated with either dimethyl sulfoxide (control) or lanosterol. The LBs' shape and opacity alterations were examined using light microscopy and mean gray value evaluation. The soluble and insoluble proteins were examined through SDS-PAGE gel electrophoresis combined with Coomassie blue staining. The protein aggregations were examined with immunofluorescence. Results: The mature LBs became cloudy with an extended culture time, and the opacification of the LBs was partially prevented by lanosterol treatment. There was less increase in insoluble proteins in the lanosterol-treated LBs than in the control group. There were also fewer cells containing aggregated protein (αA-crystallin and αB-crystallin) puncta in the lanosterol-treated LBs than in the control LBs. Conclusion: It was found that the opacification of LBs could be delayed by lanosterol treatment, which could be achieved by reducing protein aggregation, suggesting a promising HiPSC-derived drug-screening model for Age-related cataract.

Knockdown of lncRNA TUG1 protects lens epithelial cells from oxidative stress-induced injury by regulating miR-196a-5p expression in age-related cataracts.

Oxidative stress plays an important role in the pathogenesis of cataracts. Under oxidative stress, apoptosis of lens epithelial cells (LECs) is activated, which may cause lens opacity and accelerate the development of cataracts. Long non-coding RNA (lncRNA) and microRNA (miRNA/miR) are involved in cataracts. Previous studies have demonstrated that lncRNA taurine upregulated 1 (TUG1) promotes cell apoptosis induced by ultraviolet radiation by downregulating the expression of miR-421. However, the mechanism underlying TUG1 in age-related cataract remains to be elucidated. The present study aimed to investigate the effect of TUG1 in age-related cataracts and to determine the related underlying molecular mechanism. In the present study, the association between TUG1 and microRNA (miR)-196a-5p was predicted using StarBase and verified using a dual luciferase reporter assay in 293 cells. The LEC line SRA01/04 was exposed to 200 µM hydrogen peroxide (H2O2) for 24 h to establish an in vitro oxidative stress model. The mRNA expression levels of TUG1 and miR-196a-5p were analyzed using reverse transcription-quantitative PCR, whilst cell viability and apoptosis were determined using MTT and flow cytometry assays, respectively. The protein expression levels of cleaved caspase-3 and caspase-3 in SRA01/04 cells were determined using western blotting. The results of the present study revealed that TUG1 directly targeted miR-196a-5p expression. In addition, the expression levels of miR-196a-5p were downregulated in SRA01/04 cells following oxidative stress, whilst TUG1 expression was upregulated. Cell transfection with TUG1-small interfering RNA (siRNA) upregulated miR-196a-5p expression levels in SRA01/04 cells, which was reversed following co-transfection with the miR-196a-5p inhibitor. Transfection with TUG1-siRNA also reduced the levels of H2O2-induced oxidative damage in SRA01/04 cells, which was demonstrated by increased cell viability, reduced levels of apoptosis and downregulated cleaved caspase-3 levels. Conversely, transfection with the miR-196a-5p inhibitor reversed these effects aforementioned. Overexpression of miR-196a-5p reduced H2O2-induced oxidative damage in SRA01/04 cells. In conclusion, findings from the present study suggested that knocking down TUG1 expression may protect LECs from oxidative stress-induced apoptosis by upregulating the expression of miR-196a-5p.

Panel-based targeted exome sequencing reveals novel candidate susceptibility loci for age-related cataracts in Chinese Cohort.

BACKGROUND: Age-related cataracts (ARC) is the most common blinding eye disease worldwide, and its incidence tend to become younger. However, the relationship between genetic factors and mechanisms is not fully understood. The aim of the study was to further clarify the relationship between ARC and genetic mechanisms in East Asian populations and to elucidate the pathogenesis. METHODS: The study collected 191 sporadic cataracts and 208 healthy people from the eastern provinces of China, with an average age of about 60 years. All participants were subjected to a comprehensive ophthalmic clinical examination and peripheral blood samples were collected and their genomic DNA was extracted. Mutations were screened among 792 candidate genes to enhance understanding of the disease through targeted capture and high-throughput sequencing. RESULTS: We identified novel candidate susceptibility gene, which may serve as a potential susceptibility factor leading to an increase in the incidence of age-related cataracts. Three novel loci are associated with age-related cataracts significant significance: rs129882 in DBH (p = 5.27E-07, odds ratio = 3.9), rs1800280 in DMD (p = 2.85E-06, odds ratio = 1.4) and rs2871776 in ATP13A2 (p = 4.18E-05, odds ratio = 0.04). Gene-gene interaction analysis revealed that the most significant interactions between genes include the interaction between DBH and TUB (rs17847537 in TUB, rs129882 in DBH, p-value = 2.12E-14), and the interaction between DBH and DMD (rs1800280 in DMD, rs129882 in DBH, p-value = 2.12E-14). Pathway analysis shows that the most significant processes are concentrated in response to light stimulation (adjusted p-Value = 5.56E-03), response to radiation (adjusted P-Value = 5.56E-03), abiotic stimulus (adjusted p-Value = 5.56E-03). eQTL analysis shows that DBH rs129882 could regulate the expression of DBH mRNA in various tissues including retina. CONCLUSION: Our study indicates rs129882 and rs1800280 loci are associated with age-related cataracts, which enlarge the gene map of age-related cataracts.

Prevalence of Self-Reported Diagnosed Cataract and Associated Risk Factors among Elderly South Africans.

This paper estimates the prevalence of self-reported cataract and associated risk factors among individuals aged ≥50 years in South Africa. Data from a nationally-representative cross-sectional Study on Global AGEing and Adult Health (SAGE) (N = 3646) conducted in South Africa from 2007-2008 was analyzed. The primary outcome was self-reported cataract, and exposures included socio-demographics, self-reported co-morbidities, and behavioral factors. Linearized multivariate logistic regression models were used. The weighted prevalence of self-reported diagnosed cataract was 4.4% (95%CI: 3.4-5.8). Prevalence was greater among individuals with advancing age (10.2%), higher quality of life (QoL) (5.9%), education (5.2%), and wealth (5.8%) than their counterparts. Prevalence was also higher among individuals with depression (17.5%), diabetes (13.3%), hypertension (9.1%), and stroke (8.4%) compared to those without these conditions, with the exception of obesity (4.2%). In the final multivariate model, the odds of self-reported cataract were: 4.14 times higher among people ≥70 years than 50 to 59 year olds (95%CI: 2.28-7.50); 2.48 times higher in urban than rural residents (95%CI: 1.25-4.92); 5.16, 2.99, and 1.97 times higher for individuals with depression (95%CI: 1.92-13.86), hypertension (95%CI: 1.60-5.59), and diabetes (95%CI: 1.07-3.61), compared to those without these conditions.

Age-related cataracts: Role of unfolded protein response, Ca2+ mobilization, epigenetic DNA modifications, and loss of Nrf2/Keap1 dependent cytoprotection.

Age-related cataracts are closely associated with lens chronological aging, oxidation, calcium imbalance, hydration and crystallin modifications. Accumulating evidence indicates that misfolded proteins are generated in the endoplasmic reticulum (ER) by most cataractogenic stresses. To eliminate misfolded proteins from cells before they can induce senescence, the cells activate a clean-up machinery called the ER stress/unfolded protein response (UPR). The UPR also activates the nuclear factor-erythroid-2-related factor 2 (Nrf2), a central transcriptional factor for cytoprotection against stress. Nrf2 activates nearly 600 cytoprotective target genes. However, if ER stress reaches critically high levels, the UPR activates destructive outputs to trigger programmed cell death. The UPR activates mobilization of ER-Ca2+ to the cytoplasm and results in activation of Ca2+-dependent proteases to cleave various enzymes and proteins which cause the loss of normal lens function. The UPR also enhances the overproduction of reactive oxygen species (ROS), which damage lens constituents and induce failure of the Nrf2 dependent cytoprotection. Kelch-like ECH-associated protein 1 (Keap1) is an oxygen sensor protein and regulates the levels of Nrf2 by the proteasomal degradation. A significant loss of DNA methylation in diabetic cataracts was found in the Keap1 promoter, which overexpresses the Keap1 protein. Overexpressed Keap1 significantly decreases the levels of Nrf2. Lower levels of Nrf2 induces loss of the redox balance toward to oxidative stress thereby leading to failure of lens cytoprotection. Here, this review summarizes the overall view of ER stress, increases in Ca2+ levels, protein cleavage, and loss of the well-established stress protection in somatic lens cells.

The Association Between Aqueous Connective Tissue Growth Factor and the Severity of Age-related Cataracts as Graded by the Lens Opacities Classification System III.

PURPOSE: To evaluate the relationship between aqueous humor concentrations of connective tissue growth factor (CTGF) and the severity of age-related cataracts. MATERIALS AND METHODS: We conducted a prospective clinical study on 43 eyes of 43 patients with senile cataracts scheduled to undergo routine phacoemulsification surgery. Before surgery, all patients were graded for cataract severity using the Lens Opacities Classification System III in terms of four features: nuclear opalescence (NO), nuclear color (NC), cortical cataracts (C), and posterior sub-capsular cataracts (P). During surgery, aqueous humor samples were obtained from all patients, and sandwich enzyme-linked immunosorbent assays (ELISAs) were used to determine CTGF concentrations. To assess any relationship between cataract severity and CTGF levels of the aqueous humor, various correlation analyses and multiple linear regression were used. RESULTS: We found a positive correlation between the overall cataract grade and aqueous CTGF level (p < 0.05). In addition, four features of the cataract grade (nuclear opalescence, nuclear color, cortical cataract and posterior sub-capsular cataract) were positively correlated with the aqueous CTGF concentration (p < 0.05). The final regression model identified overall cataract grade as an independent predictor of increased CTGF levels in the aqueous humor (p < 0.05). CONCLUSIONS: CTGF tends to increase in the aqueous humor as the severity of age-related cataracts increases. Therefore, this cytokine may play an important role in the pathogenesis of age-related cataracts. Additional studies are required for clarification of this finding.

Generation of reactive oxygen species in the anterior eye segment. Synergistic codrugs of N-acetylcarnosine lubricant eye drops and mitochondria-targeted antioxidant act as a powerful therapeutic platform for the treatment of cataracts and primary open-angle glaucoma.

Senile cataract is a clouding of the lens in the aging eye leading to a decrease in vision. Symptoms may include faded colors, blurry vision, halos around light, trouble with bright lights, and trouble seeing at night. This may result in trouble driving, reading, or recognizing faces. Cataracts are the cause of half of blindness and 33% of visual impairment worldwide. Cataracts result from the deposition of aggregated proteins in the eye lens and lens fiber cells plasma membrane damage which causes clouding of the lens, light scattering, and obstruction of vision. ROS induced damage in the lens cell may consist of oxidation of proteins, DNA damage and/or lipid peroxidation, all of which have been implicated in cataractogenesis. The inner eye pressure (also called intraocular pressure or IOP) rises because the correct amount of fluid can't drain out of the eye. With primary open-angle glaucoma, the entrances to the drainage canals are clear and should be working correctly. The clogging problem occurs further inside the drainage canals, similar to a clogged pipe below the drain in a sink. The excessive oxidative damage is a major factor of the ocular diseases because the mitochondrial respiratory chain in mitochondria of the vital cells is a significant source of the damaging reactive oxygen species superoxide and hydrogen peroxide. However, despite the clinical importance of mitochondrial oxidative damage, antioxidants have been of limited therapeutic success. This may be because the antioxidants are not selectively taken up by mitochondria, but instead are dispersed throughout the body, ocular tissues and fluids' moieties. This work is an attempt to integrate how mitochondrial reactive oxygen species (ROS) are altered in the aging eye, along with those protective and repair therapeutic systems believed to regulate ROS levels in ocular tissues and how damage to these systems contributes to age-onset eye disease and cataract formation. Mitochondria-targeted antioxidants might be used to effectively prevent ROS-induced oxidation of lipids and proteins in the inner mitochondrial membrane in vivo. The authors developed and patented the new ophthalmic compositions including N-acetylcarnosine acting as a prodrug of naturally targeted to mitochondria l-carnosine endowed with pluripotent antioxidant activities, combined with mitochondria-targeted rechargeable antioxidant (either MitoVit E, Mito Q or SkQs) as a potent medicine to treat ocular diseases. Such specificity is explained by the fact that developed compositions might be used to effectively prevent ROS-induced oxidation of lipids and proteins in the inner mitochondrial membrane in vivo and outside mitochondria in the cellular and tissue structures of the lens and eye compartments. Mitochondrial targeting of compounds with universal types of antioxidant activity represents a promising approach for treating a number of ROS-related ocular diseases of the aging eye and can be implicated in the management of cataracts and primary open-angle glaucoma.

Association of IFN-g+874(T/A) polymorphism with female patients of age-related cataracts.

AIM: Exposure to UV light is the major risk factor in the development of age-related cataract (ARC). UV filters produced during tryptophan catabolism maintain the transparency of the lens and protect retina from photo damage. Indoleamine 2, 3-dioxygenase (IDO), the first rate-limiting enzyme in the tryptophan catabolism, is up regulated by interferon-gamma (IFN-g) which harbors single nucleotide polymorphisms (SNPs). The T allele of SNP at +874 position of the IFN-g is known to be associated with the up regulation of IDO than the allele A. Hence, we attempted to study the IFN-g+874(T/A) polymorphism for its association with ARCs. MATERIALS AND METHODS: A total of 680 cataract cases [199 nuclear (NC), 175 cortical (CC), 174 posterior subcapsular (PSC), and 132 mixed types (MT)] and 210 healthy controls were genotyped for +874(T/A) polymorphism using amplification refractory mutation system-polymerase chain reaction on 2% agarose gel stained with ethidium bromide. RESULTS: There was increased risk for CC and PSC when the patients happened to be females, with low body mass index and with early onset. Considering the IFN-g polymorphism, a high risk was observed for CC and PSC in female patients of AA genotype with significant protection for those with TT genotypes. CONCLUSION: Present results indicate that +874(T/A) polymorphism may be considered as one of the biomarkers to distinguish between the CC and PSC types of cataracts for risk estimations. The study appears to be the first of its kind reporting an association of IFN-g+874(T/A) polymorphism with ARCs.

Association of G>A transition in exon-1 of alpha crystallin gene in age-related cataracts.

AIM: To identify the presence of a known or novel mutation/SNP in Exon-1 (ex-1) of alpha crystallin (CRYAA) gene in different types of age-related cataract (ARC) patients. MATERIALS AND METHODS: Single strand Conformation Polymorphism (SSCP) analysis was carried for the detection of single nucleotide polymorphism (SNP) in ex-1 of alpha crystallin (CRYAA) gene which was confirmed by sequencing. RESULTS: The SSCP analysis of ex-1 of CRYAA gene revealed mobility shift in patients and controls, which was due to G>A transition at 6(th) position in exon-1 of CRYAA gene. All the three genotypes, GG, AA and GA, were detected in patients and controls indicating that G>A substitution is polymorphic. The analysis showed significant risk for heterozygotes (GA) as compared to pooled frequencies of homozygotes (GG + AA), which was 1.81 times for all the types of cataracts in general and 2.5 times for Nuclear Cataract and twice for Cortical Cataract. CONCLUSION: The GA heterozygotes were at higher risk for developing NC and CC types of cataracts, where as the GG homozygotes for MT and AA homozygotes for PSC types were at risk. To our knowledge, an association of G>A transition found in ex-1 of CRYAA gene with ARC, with differential risk of genotypes for individual type of cataracts has not been reported previously.