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A.V. Cideciyan, S.G. Jacobson, T.S. Aleman, D. Gu, S.E. Pearce–Kelling, A. Sumaroka, G.M. Acland, G.D. Aguirre; Dynamics of Retinal Injury and Repair After Clinical Light Exposure in the Rhodopsin Mutant Dog Model of Retinitis Pigmentosa . Invest. Ophthalmol. Vis. Sci. 2005;46(13):521.
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Purpose: Genetic and environmental factors are believed to modify the severity of human monogenically inherited retinal degenerations. This is most obvious in autosomal dominant retinitis pigmentosa (adRP) caused by rhodopsin (RHO) gene mutations; patients manifest severity differences within and between families and even within regions of the same retina. Environmental light has been suspected of contributing to this variation. Methods: Dogs heterozygous for the naturally–occuring T4R mutation in the RHO gene were used in experiments involving different doses of light. Exposed and unexposed regions were imaged with infrared SLO and optical coherence tomography (OCT) at different times ranging from 10 minutes to 6 months and retinal thickness and infrared backscattering characteristics were quantified as a function of time after exposure. Histology, immunocytochemistry and AP–1 activation assays were performed in a subset of the eyes. Results: Modest light levels used in routine fundus photography dramatically accelerated the neurodegeneration in the naturally–occurring canine model of adRP. Careful titration of the dosage of light allowed definition of the spatio–temporal sequence of retinal alterations using SLO, OCT and histopathology. A focal light exposure, equivalent in retinal irradiance to fundus photography, caused retinal alterations within minutes: there was abnormal intraretinal light backscattering along the length of photoreceptors. AP–1 activation increased within 1 hour of exposure. Progression to complete retinal degeneration occurred over ensuing weeks. Exposed wildtype and unexposed mutant retina did not change over this interval. Lower doses of light caused a slower degeneration that was delayed by 3 weeks and still incomplete by 25 weeks. There was evidence of slow repair at the edges of the exposed region, taking 9 to 25 weeks. Conclusions: Variations of disease onset and progression rate in human RHO mutations may result from a balance between success and failure of the coping responses of this genetically abnormal retina to neuronal stress from environmental light exposure. Until there is a better understanding of human retinal coping responses, it would be prudent to reduce light dose during clinical examination of adRP patients with RHO mutations.
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