Patterns of risk for diabetic retinopathy in the Mumbai slums: The Aditya Jyot Diabetic Retinopathy in Urban Mumbai Slums Study (AJ-DRUMSS) Report 3.

Diabetes onset precedes diabetic retinopathy (DR) by 5-10 years, but many people with diabetes remain free of this microvascular complication. Our aim was to identify risk factors for DR progression in a unique and diverse population, the slums of Mumbai. We performed a nested case-control study of 1163 diabetics over 40 years of age from slums in 18 wards of Mumbai. Data was collected on 33 variables and assessed for association with DR using both univariate and multivariate analyses. Stratified analyses were also performed on males and females, separately. Among hypertensive individuals we also assessed whether duration of hypertension associated with DR. Of 31 non-correlated variables analysed as risk factors for DR, 15 showed evidence of significant association. The most prominent included sex, where being a female associated with decreased odds of DR, while longer duration of diabetes and poor glycaemic control associated with increased odds. The duration of diabetes effect was partially, but significantly, mediated by age of diabetes diagnoses (8.6% of variance explained, p = 0.012). Obesity as measured by several measures, including body mass index (BMI) and measures of central obesity had a negative association with DR; increased measures of obesity consistently reduced odds of DR. As in most earlier studies, DR was associated with the duration of diabetes and glycaemic control. However, other factors, especially obesity related measures were associated with DR, in ways that contrast with most prior studies. These results indicated that the overall pattern of association in the Mumbai slums was novel. Thus, in previously uncharacterized populations, such as the slums that we examined, it is important to evaluate all risk factors de novo to appropriately assess patterns of association as the patterns of association with DR can be complex and population specific.

Deciphering the association of intronic single nucleotide polymorphisms of crystallin gene family with congenital cataract.

Purpose: Introns play an important role in gene regulation and expression. Single nucleotide polymorphisms (SNPs) in introns have the potential to cause disease and alter the genotype-phenotype association. Hence, this study aimed to decipher the association of SNPs in the introns of the crystallin gene in congenital cataracts. Methods: SNPs in the introns of crystallin gene family - CRYAA (rs3788059), CRYAB (rs2070894), CRYBA4 (rs2071861), and CRYBB2 (rs5752083, rs5996863) - were genotyped in 248 participants consisting of 141 congenital cataracts and 107 healthy controls by allele-specific oligonucleotide polymerase chain reaction method. Around 10% of samples for each SNPs were sequenced to confirm the genotypes. The allele, genotype, and haplotype frequency were evaluated by the SHEsis online tool. Results: Using dominant model, the "A" allele of rs3788059 was found to have an increased risk toward congenital cataract development whereas the "G" allele was found to be protective (AA + AG vs. GG; odds ratio [OR] 95% confidence interval [CI] = 3.73 [1.71, 8.15], P = 0.0009). The "A" allele of both rs2070894 (AA + AG vs. GG; OR [95% CI] = 0.49 [0.29, 0.84], P = 0.012) and rs5752083 (AA + AC vs. CC; OR [95% CI] = 0.25 [0.08, 0.76], P = 0.016) were suggested to have a protective role by the dominant model. The A-C-T haplotype (rs2071861, rs5752083, and rs5996863) was found to be a significant risk factor for the development of congenital cataract. Conclusion: Intronic SNPs in crystallin genes may play a role in the predisposition toward congenital cataract. However, the present findings need to be replicated in a large cohort with more number of samples.

Protective association of A-T-T haplotype of DMT1 gene against risk of human age-related nuclear cataract.

BACKGROUND: Age-related cataract (ARC) is profoundly associated with oxidative stress. Iron plays a pivotal role in generating oxidative stress and promoting deleterious irreversible damage to the macromolecules. Divalent metal transporter 1 (DMT1) mediates the uptake of iron into the cell. Aberrant transcript expression of DMT1 gene in lenses of human ARC was reported. The present investigated the genetic association between DMT1 gene polymorphisms and risk of ARC. METHODS: DNA from peripheral blood of ARC subjects (n = 764) and age-matched controls (n = 794) was isolated. Genotyping of three single-nucleotide polymorphisms (SNPs) - rs224589 (C/A), rs1048230 (T/C), and rs2285230 (T/C) - of DMT1 gene was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism technique. Level of DMT1 transcript expression was determined by quantitative real-time PCR analysis using RNA from lens epithelial and fiber cells. RESULTS: Nuclear cataract showed a higher frequency of CC genotypes (OR = 1.40; 95%CI = 1.01-1.95; p = 0.04) of SNP rs224589 and a significantly lower frequency of A-T-T haplotype (OR = 0.63; 95%CI = 0.42-0.92; p = 0.02) than that of controls. The A-T-T haplotype demonstrated a dominant protective effect against disease risk when compared to the more common haplotype (C-T-T) (p = 0.01). The haplotype pairs C-T-T/C-T-T and A-C-C/A-C-C showed higher level of transcript expression of DMT1 than C-T-T/A-T-T haplotype pair (p < 0.05). Further, a novel genetic variation (c.1328A>G; p.N443S) in exon 3 of DMT1 gene was observed in a subject with nuclear cataract. CONCLUSIONS: The results highlighted a protective association of A-T-T haplotype against the risk of ARC.

wound healing activity of Morinda tinctoria Roxb aqueous leaf extract.

This study investigated the wound healing properties of the aqueous extract of Morinda tinctoria Roxb leaves in rats. The study also provides information on the purification, qualitative, and quantitative analysis of phytochemical components present in M. tinctoria Roxb. Wound contraction and period of epithelialization was determined and topical application of M. tinctoria Roxb aqueous leaf extract showed better healing than orally treated and control groups. The results suggest that the efficacy of M. tinctoria Roxb aqueous leaf extract as a wound healing agent and can also be used as a therapeutic agent for internal as well as external wounds.

A Prospective Evaluation of Posterior Capsule Opacification in Eyes With Posterior Capsule Plaque-A Case-Control Study.

PURPOSE: To compare the development of posterior capsule opacification (PCO) between eyes with and without posterior capsule plaque after single-piece hydrophobic acrylic intraocular lens (IOL) implantation 5 years postoperatively. DESIGN: A prospective observational case-control study. METHODS: One hundred one consecutive eyes with posterior capsule plaque (cases) were compared with the same number of cataractous eyes without posterior capsule plaque (controls). A detailed preoperative evaluation was done to detect the presence of posterior capsule plaque. Histomorphology of posterior capsule plaque was evaluated. Postoperatively, digital retroillumination photographic documentation was performed at 1 month and 1, 2, 3, and 5 years and analyzed for PCO using the Evaluation of Posterior Capsule Opacification (EPCO) software; EPCO scores and areas were calculated. The development of PCO and the influence of the anterior capsule cover (total and partial) on the IOL optic were compared. RESULTS: Posterior capsule plaque on histomorphology showed a large amount of collagenous, fibrous extracellular matrix, and immunofluorescence staining was positive for alpha smooth muscle actin. In the development of PCO, there was no difference between cases and controls at 1 month and 1, 2, 3, and 5 years. Between the 2 groups, there was no difference in the development of PCO within total cover and within partial cover of the anterior capsule on the IOL up to 5 years. CONCLUSIONS: The presence of posterior capsule plaque did not increase the incidence of PCO at 5 years.