The Polymorphisms with Cataract Susceptibility Impair the EPHA2 Receptor Stability and Its Cytoprotective Function.

ABSTRACT: Despite accumulating evidence revealing susceptibility genes for age-related cataract, its pathophysiology leading to visual impairment at the cellular and molecular level remains poorly understood. Recent bioinformatic studies uncovered the association of two single nucleotide polymorphisms in human EPHA2, rs2291806 and rs1058371, with age-related cataract. Here we investigated the role of EPHA2 in counteracting oxidative stress-induced apoptosis of lens epithelial cells. The cataract-associated missense mutations resulted in the destabilization of EPHA2 receptor without altering the mRNA transcription. The cytoprotective and antiapoptotic function of EPHA2 in lens epithelial cells was abolished by the functional polymorphisms. Furthermore, our results suggest that the downstream signalin

SUBMITTER: Yang J 

PROVIDER: S-EPMC4668318 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature