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Journal of Ophthalmology
Volume 2015, Article ID 401894, 9 pages
Research Article

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

Jin Yang,1,2 Dan Li,2,3 Qi Fan,1,2 Lei Cai,1,2 Xiaodi Qiu,1,2 Peng Zhou,4 and Yi Lu1,2

1Department of Ophthalmology, Eye and ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, China
2Myopia Key Laboratory of Health PR China, Shanghai 200031, China
3Research Center, Eye and ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, China
4Department of Ophthalmology, Parkway Health Hong Qiao Medical Center, Shanghai 200336, China

Received 27 June 2015; Revised 20 October 2015; Accepted 22 October 2015

Academic Editor: Jun Zhang

Copyright © 2015 Jin Yang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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 signaling of activated EPHA2 promotes the antioxidative capacity of lens epithelial cells to eradicate the overproduction of reactive oxygen species. In contrast, the overexpression of EPHA2 with nonsynonymous mutations in the lens epithelial cells offered limited antioxidative protection against oxidative stress. Thus, our study not only sheds the light on the potential cytoprotective function of EPHA2 signaling in lens but also provides the cellular mechanisms underlying the pathogenesis of age-related cataract.