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Sten Kjellstrom, Ronald Bush, Yong Zeng, Paul Sieving; Dim light rearing slows the decline in post-photoreceptor function in the Rs1-KO mouse. Invest. Ophthalmol. Vis. Sci. 2013;54(15):714.
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Retinoschisin knockout (Rs1-KO) mice have a progressive decrease in the ERG a-wave and a more rapid decline in the b-wave, indicating a loss in both photoreceptor and post-photoreceptor cell function. This is accompanied by photoreceptor degeneration and the formation of schisis cavities in the outer plexiform (OPL) and inner nuclear (INL) layers. Previous studies in animal models have shown that bright light exposure exacerbates and dark rearing ameliorates photoreceptor degeneration in animal models. We investigated whether light rearing intensity affects the progression of pathology in the Rs1-KO mouse.
Rs1 mice and wild type mice (WT) were maintained from birth in 200 lux (BL) or 20 lux (DL) cyclic light. The ERG was recorded at 1 and 4 months. The extent of schisis cavities was monitored in vivo by measuring OPL and INL area using optical coherence tomography (OCT).
At 1 month, the a-wave and b-wave amplitudes in DL reared (n=36 eyes) Rs1-KO mice were not significantly different from BL reared mice (n=24 eyes). However, by 4 months, the b-wave amplitude in BL reared Rs1-KO mice was significantly lower than in DL reared mice (p<0.0001, n= 35 and 37 eyes, respectively). The a-wave amplitudes Rs1-KO mice reared in DL and BL were not different at 4 months, so the b-/a-wave ratio was greatly reduced in BL mice compared to DL mice (1.76 vs. 1.17, p<0.0001). At 4 months, the extent of schisis cavities was greater in BL reared Rs1-KO mice than in DL reared mice as indicated by a significantly larger INL+OPL area (p<0.0001, n=33 and 23 eyes, respectively). There were no differences in ERG amplitudes between DL and BL reared WT mice at either age.
Dim light rearing did not rescue the a-wave in Rs1-KO mice, but it did rescue the b-wave and post-photoreceptor structure. Unlike other models of photoreceptor degeneration, light rearing intensity modulates the natural history of both functional and structural inner retinal pathology in Rs1-KO mice without an effect on photoreceptor function. In addition to gene therapy, this is a second example of the rescue of inner retinal structure and function in the adult Rs1-KO mouse.
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