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Micah A Chrenek, Sarah Warren Gooding, Jana Terrell Sellers, Robin H Schmidt, Nathaniel F Henneman, Preston E Girardot, Jeffrey H Boatright; Comparison of the RHO-tvrm4 and light damage models of retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2017;58(8):615. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The RHO-tvrm4 mouse strain is a genetic model of retinitis pigmentosa that allows coordinated retinal degeneration induced by very brief exposure to bright light. Our results suggest that the underlying mechanisms by which photoreceptors die and the stress response in the retina is similar to the light induced retinal damage (LIRD) model of retinal damage. Here we describe a time course of retinal degeneration in both models and what the effects are in retinal and RPE morphology, inflammation response, and complement deposition.
LIRD was performed by exposing BALB/cAnNCrl mice (60-100 days old) to 5000 lux of white LED light for 4 hours or 129S2/SvPasCrl (100 days old) dilated with atropine and exposed to 30000 lux of white LED light for 4 hours. C57BL6/J RHOtvrm4/+ were exposed to 50000 lux of white light for 5 min without atropine to induce retinal degeneration. Mice were sacrificed 7 or 8 days following induction and eyes collected for immunohistochemistry and retinas for RNA isolation. Gene expression analysis was performed at 2 and 7 or 8 days following damage for candidate genes using digital droplet PCR. TUNEL staining was performed to determine the time course of loss of photoreceptors. Immunostaining was performed on retinal sections for complement components and stress markers. RPE flatmounts were stained with ZO1 and analyzed at 3 days following damage to determine effects on RPE morphology and images analyzed with Cell Profiler software.
A significant induction of complement components including C1QA, C1QB, C3, CFB, and CFH were present 2 and 7 or 8 days after damage occurred in both models. Stress related genes including HMOX1, HIF1A, and LIF showed similar inductions in both models. A much greater proportion of the photoreceptors were TUNEL-positive in the LIRD model than in the RHO-tvrm4 model at 2 days. RPE flatmount morphology measurements, including cell area and eccentricity, were significantly disrupted in LIRD 129sv mice as early as 2 days following light exposure and in RHO-tvrm4 mice as early as 3 days following light induction.
The RHO-tvrm4 genetic model of retinitis pigmentosa shows similar degeneration effects as the LIRD BALB/c and 129sv models. The RHO-tvrm4 model allows for the use of C57BL/6J background mice to assess the effects of available transgenic mutations without crossing them into the BALB/c background.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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