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Stefania Marsili, Jeremy Gingrich, Gustavo D. Aguirre, William A. Beltran; Role of Endoplasmic Reticulum (ER) Stress Following Light Exposure in the Canine T4R RHO Mutant Model. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2561.
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© ARVO (1962-2015); The Authors (2016-present)
The canine T4R RHO model of autosomal dominant retinitis pigmentosa shows extreme sensitivity to light. Brief exposure to light levels commonly used in clinical settings leads to acute death of rod photoreceptors that can be detected 6 hours after exposure. The purpose of this study is to assess the role of the unfolded protein response (UPR) induced endoplasmic reticulum stress in light induced retinal degeneration in the T4R RHO model.
Three heterozygous mutant (RHOT4R/+), and three wild type (RHO+/+) dogs (ages: 12-24 weeks) were used. Following overnight dark adaptation, left eyes were exposed to bright white light (corneal irradiance: 1mW/cm2) for 60s; right eyes were shielded and used as negative control. Six hours following light exposure, neuroretinas were collected under dim red light, snap-frozen in liquid nitrogen, and subsequently processed for Western Blot analysis. Twenty or forty micrograms of whole retinal tissue lysates were used to detect the levels of the following stress-induced proteins: HSP70, HSF1, BIP/Grp78, PDI, calnexin, ATF4. Beta-actin or α-tubulin were used as internal controls for normalization.
No differences in protein expression levels of ER-resident (BIP/Grp78, PDI, calnexin) and cytoplasmic (HSP70, HSF1) chaperones were found between exposed and shielded retinas. Additionally, activation of the PERK-ATF4 ER stress signaling pathway was not observed at the time point studied.
Preliminary results do not indicate the involvement of a UPR 6 hours post light exposure in the T4R RHO mutant canine retina. On-going studies are evaluating the role of the two other ER stress pathways downstream of the ATF6 and IRE1 ER sensors. In addition, the occurrence of ER stress is being examined at earlier and later time points following light exposure.
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