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Paediatric cataract: is there any role for studying the gene expression?

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Session Details

Session Title: Cataract Surgery Paediatric/Complications/Management

Session Date/Time: Monday 09/10/2017 | 16:30-18:00

Paper Time: 16:30

Venue: Room 4.1

First Author: : J.Matalia INDIA

Co Author(s): :    S. Shanbagh   V. Rajput   A. Ghosh   B. Shetty           

Abstract Details

Purpose:

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 classified pediatric cataract into an etiological and morphological classification for the purpose of the study and established 8 distinct groups. In this prospective study, we evaluate the expression of pro-fibrotic factors (genes maintaining integrity of lens), lens structural proteins (genes related to maintain transparency of the lens) and developmental transcription factors (genes playing a role in lens development) in phenotypically & etiologically distinct forms of pediatric cataract.

Setting:

Narayana Nethralaya, a tertiary eye care center and teaching institute, Bangalore, India.

Methods:

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-3(FOXE3), Pituitary homeobox-3(PITX-3) and pro-fibrotic genes: Transforming growth factor beta-β(TGF-β), Alpha Smooth muscle actin(α-SMA), Bone morphogenetic protein-7(BMP-7) & Vimentin

Results:

Pearson correlation was done for determining statistical significance of gene expression in each group. The pprenatal cataracts were likely derived from the problems in structural genes (correlated with p=0.02, p=0.001 and p=0.003) that could be genetic in nature. The infectious cataract show different profile of a high transcriptional activity with the cytomegalovirus having the highest expression of all factors (correlated with p=0.003, p= 0.006 and p=0.04) as compared to rubella (correlated with p=0.001, p=0.02, p=0.04). The results show that there is evidence of TGF-β driven profibrotic mechanism (correlated with p=0.002 and p=0.001) leading to cataract formation in postnatal cataract.

Conclusions:

This is the first report on gene expression in pediatric cataracts that illustrates differences in biological pathways leading to cataract subtypes with functional correlation. A specific trend of gene expression was noted in the different groups of cataract. We also provide a systematic pediatric cataract phenotypic classification and its correlation with the molecular expression patterns. This study shows that the molecular mechanisms are different in different types of cataract with upregulation of all the genes in infectious CMV cataract while it is down regulated in cataracts with posterior capsular anomalies and traumatic cataract.

Financial Disclosure:

NONE

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