Research Projects

Pseudoexfoliation is the leading cause of secondary glaucoma with its prevalence being 21% in the Nordic countries. In India PEX prevalence is 3.8% which increases to 6.2% in individuals aged above 60 years. The etiology of PEX is multifactorial with numerous genome-wide association studies and candidate genes identifying many genetic risk factors for PEX. But the results are inconclusive in context of disease causation and progression due to incomplete penetrance and allele reversals across different ethnicities. As PEX progresses with age, an involvement of epigenetic regulation in PEX pathology is highly anticipated but a systematic epigenome-wide study is yet to be carried out. Epigenetic marks are reversible changes that are influenced by environmental factors resulting in aberrant gene expression. Thus, they provide a mechanism for interplay between genetic and environmental effects in a disease pathophysiology. Only a few studies have reported an association between epigenetic changes and PEX pathology. We have also very recently found hypermethylation in HSP70 gene leading to a decrease in its expression. In absence of proper understanding of most of the risk factors for disease causation, all previous attempts to create an animal model for PEX and developing a biomarker for early detection of the disease have failed. This innovative proposal aims to identify global DNA methylation signatures in PEX affected individuals through epigenome-wide association study and correlate the disease associated CpG methylation markers with differential gene expression and integrative analysis. The study will be conducted using the affected tissue, lens capsule as specimen from 60 PEXS, 60 PEXG and 60 age-sex matched control subjects and later validated in peripheral blood so as to identify novel markers for early prediction of the disease and differential markers between the two stages of PEX. Also, this would be the first study undertaken to identify global DNA methylation markers and their correlation with gene expression in PEX that will unravel novel associated genes, the underlying pathways and mechanisms leading to the disease pathology thus providing a way towards curtailing the disease.