Photoreceptor Pathology Following Clinical Light Exposure in the T4R Rhodopsin (RHO) Mutant Dog

Abstract

Abstract: : Purpose: To examine the photoreceptor pathology in RHO mutant dogs following full–field or focal light illumination. Methods: Age–matched, dark adapted T4R+/– and wt dogs were exposed to either focal (3mm diameter) or full field illumination using light levels comparable to those used in clinical fundus photography, and enucleated at selected time points after exposure. Topographic maps of the disease distribution were reconstructed from sequential fields of plastic sections that extended from the disc to the ora serrata. Results:Abnormalities were found by 2 hours following exposure; there was massive OS shedding, and the ROS were short, disorganized and fragmented. Edema and pyknosis in the ONL were present. By 24 hours the photoreceptor changes were more advanced, and RPE cells were reactive and migrated into subretinal space. With time, there was photoreceptor loss; the RPE was absent or markedly abnormal in those areas where it remained. Topographic maps of the disease distribution showed that retinal pathology was localized to the exposed regions with focal illumination, but there was widespread degeneration that extended almost into the periphery with full field exposures. Conclusions: Exposure of dark–adapted T4R RHO mutant dog retinas to light levels comparable to that used in fundus photography resulted in a rapid onset of photoreceptor degeneration. The exposure also damages the RPE, and may account for the secondary cone degeneration observed. A combination of genetics and environment results in the observed retinal degeneration phenotype.

Keywords: retinal degenerations: hereditary • retinal degenerations: cell biology • photoreceptors