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Jyoti Matalia, Shaika Shanbagh, Vimal Krishna Rajput, Rajni Kantha, Arkasubhra Ghosh; Distinct signaling networks in lens tissue drives phenotypically & etiologically diverse forms of pediatric cataract. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Pediatric cataract is a major cause of preventable childhood blindness worldwide. Although various mutations have been identified in familial studies, the mechanistic basis of cataract development remains poorly understood. We evaluate the expression of pro-fibrotic factors, structural proteins and developmental transcription factors in phenotypically & etiologically distinct forms of pediatric cataract
Lens material was sampled during routine pediatric cataract surgery (n=53) with prior approval of the Institutional Ethics Committee and written informed consent. We established 8 groups [prenatal infectious (cytomegalovirus, rubella and combined cytomegalovirus with rubella infection), prenatal non-infectious, posterior capsular anomalies, postnatal, traumatic, secondary] which were compared to clear, non-cataractous lenses(n=6). Expression levels were measured for lens structure related genes: Aquaporin 0(Aqp-0), Heat Shock protein 4(HSPA4), Crystallin gamma C(CRYGC), lens developmental transcription factors: Musculoaponeurotic fibrosarcoma oncogene(MAF), Tumor domain containing 7(TDRD 7), Forkhead box(FOXE3), Pituitary homeobox 3(PITX-3) and pro-fibrotic genes: Transforming growth factor beta(TGF-β), Alpha Smooth muscle actin(α-SMA) and Vimentin, Bone morphogenetic protein-7(BMP-7). Pearson correlation was done for determining statistical significance of gene expression in each group
A specific trend of gene expression was noted in different groups of cataract. The prenatal cataracts were likely derived from the problems in structural genes that could be genetic in nature. The postnatal cataracts show evidence of TGF-β driven profibrotic processes that lead to cataract. The infectious cataracts show different profile with high transcriptional activity, particularly in CMV infections as compared to rubella
This is the first report on gene expression in pediatric cataracts that illustrates differences in biological pathways leading to cataract subtypes with functional correlation. We also provide a systematic pediatric cataract phenotypic classification and its correlation with the molecular expression patterns. It may eventually find its clinical application in early detection and management of pediatric cataract
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
Network of diseases and significantly (Pearson correlation <0.05) co-expressed genes correlated to enriched biological processes
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