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Micah A Chrenek, Jana T Sellers, Preston Girardot, J M Nickerson, Porfirio Nava, Jeffrey H Boatright; RHO-tvrm4 mice lacking STAT2 are resistant to light induced retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3047. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The RHO-tvrm4 mouse undergoes retinal degeneration following a brief exposure to bright light [Budzynski et al.,2010]. STAT2 is a key transcription factor that induces IL6 and drives the activation of macrophages. Our previous work has shown that knockout of STAT2 is protective in a model of inflammatory bowel disease. We hypothesized that STAT2 knockout would also be protective in the RHO-tvrm4 model.
STAT2 knockout mice (stock 023309) were obtained from The Jackson Laboratory and crossed with RHO-tvrm4 mice (stock 029087). Mice homozygous for STAT2 knockout and heterozygous for RHO-tvrm4 (“STAT2-KO“) were generated. Mice were dark adapted overnight and given atropine eye drops. The mice were exposed to 6000 lux of bright light for 5 min to induce retinal degeneration and then returned to cyclic light conditions. One week after light induction, visual function (spatial frequency threshold; SFT) and retinal function were assessed by optomotor response (OMR) and electroretinogram (ERG). Retinal structure at the posterior of the eyes was also assessed by OCT.
Photoreceptor function as assessed by ERG scotopic a-waves were equal in STAT2-WT and STAT2-KO mice without light induction. With light induction, a-wave response of STAT2-WT mice was reduced to 40.4% of dim controls whereas in STAT2-KO it was reduced to 67.5%.OCT measurement of photoreceptor layer (PRL) thickness showed no difference between the dim control groups (STAT2-WT 103.9 um+/-0.8, STAT2-KO 102.9+/-0.9 um). After light induction, STAT2-WT mice PRL was 38.7+/-8.8 um whereas in STAT2-KO mice it was 80.4+/-5.1 um.Visual function as measured by SFTs was equivalent between STAT2-WT and STAT2-KO exposed to dim light. Compared to their control cohorts exposed to dim light, after light induction, the visual function of STAT2-WT mice declined, but that of STAT2-KO did not significantly change.
Knockout of STAT2 diminished retinal degeneration and function loss in light induced RHO-tvrm4 mice. With light induction in RHO-tvrm4 mice, knockout of STAT2 provided 45% protection of photoreceptor function as assessed by ERG. In measurements of PRL, knockout of STAT2 provided 65% protection. OMR results trended towards showing better visual function in the STAT2-KO than STAT2-WT mice after light induction. We conclude that STAT2 is involved in retinal degeneration.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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