UPR Activation and the Down-Regulation of α-Crystallin in Human High Myopia-Related Cataract Lens Epithelium

Purpose To investigate the expression of alpha A- and alpha B-crystallin and the unfolded protein response in the lens epithelium of patients with high myopia-related cataracts. Methods and Materials The central portion of the human anterior lens capsule together with the adhering epithelial cells, approximately 5 mm in diameter, were harvested and processed within two hours after cataract surgery from high myopia-related (spherical equivalent >=-10.00 diopters) and age-related cataract patients or from high myopia but non-cataractous patients (tissue were collected from ocular trauma patients with high myopia and lens trauma). Anterior lens samples from fresh cadaver normal human eyes were used as normal control (collected within 6 hours from death). Real-time PCR was performed to detect the mRNA levels of alpha-crystallins as well as unfolded protein response (UPR)-related GRP78, spliced-XBP1, ATF4 and ATF6. Western blot analysis was used to determine the protein level of alpha-crystallin, GRP78, p-IRE1 alpha, p-eIF2 alpha and ATF6. Results In the lens epithelium of the high myopia-related cataract group and the age related cataract group, the mRNA and soluble protein expression of alpha A- and alpha B-crystallin were both decreased; additionally, the protein levels of ATF6, p-eIF2 alpha and p-IRE1 alpha and the gene expression levels of spliced XBP1, GRP78, ATF6 and ATF4 were greatly increased relative to the normal control. Conclusion These results suggest the significant loss of soluble alpha-crystallin and the activation of the UPR in the lens epithelium of patients with high myopia-related cataract, which may be associated with the cataractogenesis of high myopia-related cataract.