This study is intended to investigate the epigenetic regulation of the most conserved molecular chaperone, HSP70 and its potential role in the pathophysiology of pseudoexfoliation syndrome (PEXS) and glaucoma (PEXG), a protein aggregopathy, contributing significantly to world blindness. Expression levels of HSP70 were significantly decreased in the lens capsule (LC) of PEXS but not in PEXG compared with that in control. Bisulfite sequencing of the LC of the study subjects revealed that the CpG islands (CGIs) located in the exonic region but not in the promoter region of HSP70 displayed hypermethylation only in PEXS individuals. There was a corresponding increase in DNA methyltransferase 3A (DNMT3A) expression in only PEXS individuals suggesting de novo methylation in this stage of the disease condition. On the other hand, peripheral blood of both PEXS and PEXG cases showed hypermethylation in the exonic region when compared with non-PEX controls displaying tissue-specific effects. Further, functional analyses of CGI spanning the exon revealed a decreased gene expression in the presence of methylated in comparison with unmethylated reporter gene vectors. Treatment of human lens epithelial B-3 (HLE B-3) cells with DNMT inhibitor restored the expression of HSP70 following depletion in methylation level at exonic CpG sites. In conclusion, a decreased HSP70 expression correlates with hypermethylation of a CGI of HSP70 in PEXS individuals. The present findings enhance our current understanding of the mechanism underlying HSP70 repression, contributing to the pathogenesis of PEX.
March 13, 2020
Challenges to accomplish stringent fluid management standards 7 years after enhanced recovery after surgery implementation-The surgeon’s perspective.
March 5, 2020
- ACC 2020The American College of Cardiology decided to cancel ACC.20/WCC due to COVID-19, which was scheduled to take place March 28-30 in Chicago. However, ACC.20/WCC Virtual Meeting continues to release cutting edge science and practice changing updates for cardiovascular professionals on demand and free through June 2020.
- ENDO: 2020ENDO 2020 Annual Conference has been canceled due to COVID-19. Here are highlights of emerging data that has still been released. Keep an eye out for ENDO Online 2020, which will take place from June 8 to 22.