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T. Nakanishi, S. Imai, Y. Inokuchi, K. Tsuruma, M. Shimazawa, Y. Monguchi, H. Sajiki, T. Kudo, H. Hara; The Effect of an Inducer of Bip, an ER-Resident Molecular Chaperone, on Light-Induced Retinal Damages. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2255.
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Recent evidence suggests that endoplasmic reticulum (ER) stress is activated during light-induced retinal damage. A preferential inducer of 78 kDa glucose-regulated protein (GRP78)/immunoglobulin binding protein (BiP; Bip inducer X, BIX) has the protective effect against ER stress-induced cell death. Here, we investgated changes of ER stress-related factors in retina after the light exposure and effect of BIX on light-induced retinal cell death in mice.
To examine the ER stress activation, we measured time-dependent changes of ER stress-related factors in retina after light exposure using quantitative RT-PCR: The expressions of GRP78/BiP, C/EBP-homologous (CHOP), calreticulin, ER degradation enhancing α-mannosidase like protein (EDEM), asparagine synthetase (ASNS), 94 kDa glucose-regulated protein (GRP94), and 52 kDa repressor of the inhibitor of the protein kinase (p58IPK) were measured. Retinal light damage was induced by exposure to constant white fluorescent light for 3 h at an illumination of 8000 lux. To evaluate the effect of BIX on retinal damages, a- and b-wave amplitudes of the dark-adapted electroretinogram (ERG) were recorded at 5 days after light exposure, then outer nuclear layer (ONL) thickness was measured on hematoxylin-eosin-stained sections. BIX (5 nmol/eye) was intravitreously injected at 6 h before light exposure.
RT-PCR revealed that all ER stress-related factors except ASNS were increased after light exposure. The a- and b-wave amplitudes of the dark-adapted ERG were reduced at 5 days after light exposure, and BIX treatment significantly prevented the retinal dysfunctions as compared with those in vehicle-treated group. In histological analysis, the light exposure reduced ONL thickness, and treatment with BIX significantly inhibited the ONL atrophy as compared with that in vehicle-treated group.
These data indicate that ER stress may play a pivotal role in light exposure-induced retinal damage, and treatment with BIX may prevent the retinal damage.
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