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2015 ; 10
(9
): e0137582
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UPR Activation and the Down-Regulation of ?-Crystallin in Human High
Myopia-Related Cataract Lens Epithelium
#MMPMID26351848
Yang J
; Zhou S
; Gu J
; Guo M
; Xia H
; Liu Y
PLoS One
2015[]; 10
(9
): e0137582
PMID26351848
show ga
PURPOSE: To investigate the expression of ?A- and ?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 ?-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 ?-crystallin, GRP78, p-IRE1?, p-eIF2? 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 ?A- and ?B-crystallin
were both decreased; additionally, the protein levels of ATF6, p-eIF2? and
p-IRE1? 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 ?-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.