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Glaucoma is a neurodegenerative ophthalmic disorder and is considered among the leading causes of irreversible blindness. Primary open-angle glaucoma (POAG) is the most common type of glaucoma that affects after 30 years of life, progressing slowly, and manifests as decreased visual acuity leading to blindness if not treated. POAG is genetically heterogeneous, inherited most commonly in autosomal dominant mode. Several genes have been reported for POAG with myocilin (Myoc) being most common. The present study has been conducted to screen 25 POAG families with 2 or more affected members for their association with Myoc and CYP1B1 (the most common gene in primary congenital glaucoma). After approval from Institutional Ethical Review Committee (ERC), 25 POAG families were enrolled from the southern province (Sindh) of Pakistan. Written informed consent was obtained from all participating individuals and diagnosis was confirmed by consultant ophthalmologists using various instruments and means. Venous blood was obtained from affected individuals and their normal family members for DNA extraction and subsequent analysis. All samples were initially screened for the Myoc gene followed by CYP1B1. Screening for Myoc revealed one previously reported variant c.144G>T in POAG-06 whereas screening for CYP1B1 in all 25 families showed a novel variant c.649G>A in POAG-02. The pathogenicity of the novel variant was confirmed using various bioinformatics tools. This is the first report of any POAG family found associated with a novel variant in CYP1B1 from the southern province of Pakistan whereas one family found associated with a reported variant in Myoc. The remaining 23 POAG families did not found to be associated with either Myoc or CYP1B1 indicating genetic heterogeneity of the population in this part of the world. [ABSTRACT FROM AUTHOR]

Abstract: Maternal diseases like diabetes mellitus may cause developmental defects. Supplementation with folic acid and vitamin C during the periconceptional period has been shown to prevent some neural tube and congenital heart defects. Hearts were dissected from 5 days-old White Leghorn chick embryos, the cells isolated and cultured in micromass under diabetic conditions, with and without folic acid and vitamin C. Contractile activity, cell viability (resazurin reduction) and protein assays were performed. Results indicated diabetic conditions reduced contractile activity and cell viability, whilst vitamin C (100μM) and folic acid (1mM) administered concurrently significantly improved them to values comparable with the control. Day 3 chick embryos in ovo were injected with glucose+hydroxybutyrate or a combination of these and vitamins. Diabetic conditions caused gross and histological malformations, but these effects were abrogated by vitamin supplement. Teratogenic effects on heart development could possibly be prevented by vitamin supplementation during pregnancy. [Copyright &y& Elsevier]

Abstract: The teratogenic effects of ethanol include malformations of the cardiovascular system, which may be abrogated by multivitamin therapy. Chick cardiomyocytes in micromass culture were treated with ethanol alone or with supplementation with folate or vitamin C. Ethanol alone caused a loss of cell viability and differentiation (beating) whereas those cells treated in addition with vitamins were comparable to the control. Chick embryos were injected on day 3 of incubation with PBS, ethanol alone or with additional vitamin C or folic acid. On day 9 embryos were examined for viability, growth retardation and gross malformation and the hearts were processed for histology. Results showed that ethanol significantly decreased survival of embryos or caused growth retardation and gross malformation (p <0.05). Embryos incubated with addition of vitamin C or folic acid were comparable to the control. Data obtained in this study suggest that supplementation with vitamin C or folic acid during pregnancy may prevent defects in heart development brought about by ethanol. [Copyright &y& Elsevier]