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D. A. White, M. P. Krebs, S. Kaushal; Time Course of Cone Cell Degeneration Following Light Damage in the T17M Mouse Model of ADRP. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4416.
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To examine cone photoreceptor cell damage and to further resolve the temporal course of light-induced retinal damage in the rho+/-; hT17M mouse model of ADRP, as well as other mouse models of retinal disease.
Mice were exposed to 15,000 lux white light in their right eyes for 2.5 minutes. ERG measurements were performed at subsequent intervals to determine the time course of degeneration for both scotopic and photopic responses. Histology was performed to examine rod and cone photoreceptor cell death, and to visualize other changes in retinal morphology in response to light damage.
rho+/-; hT17M mice showed a dramatic loss of scotopic ERG response as early as 12 hours following light exposure, with almost complete loss of scotopic function by 24 hours. In contrast, photopic responses were of normal amplitude at 24 hours, with only a slight loss of a-wave response and a reproducible delay in the implicit time-to-maximum of the response. Loss of amplitude of the photopic response was observed starting at 48 hours following light exposure; maximum loss of photopic response was seen at 96 hours following light exposure. PNA stains of retinal flat mounts revealed significant disruption of cone photoreceptor morphology at as early as 24 hours after light exposure, while TUNEL stained thin sections revealed photoreceptor apoptosis 24 hours after light exposure. ERG responses of non-transgenic littermate mice, as well as other mouse models of retinal disease, and also the Balb/c mouse, were not affected by this light regime.
We observe both functional and structural evidence of photoreceptor damage in hT17M+mutant mice exposed to 15,000 lux white light for 2.5 minutes. The damage initially affects the scotopic ERG response, and later includes loss of both scotopic and photopic responses. Interestingly, significant disruption was noted in cone cell morphology as early as 24 hours, even though there was only a slight change in photopic response at this point. Also, other mouse models were tested and found to be unaffected by this light damage regime, signifying, among other things, a difference between the T17M phenotype and the previously reported Balb/c light sensitivity.
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