SUBRETINAL PIGMENT EPITHELIAL DEPOSITS IN A DOMINANT LATE-ONSET RETINAL DEGENERATION

Purpose. To determine the pathogenesis of an autosomal dominant late-o nset retinal degeneration by studies of the retinal histopathology, ph enotype of family members, and candidate genes for the disease. Method s. The retina from an 80-year-old patient donor was prepared for Light and electron microscopy, including special stains and immunocytochemi stry. Family members were examined clinically and with retinal functio n tests. Rhodopsin, peripherin/RDS, and TIMP3 genes were screened for mutations, and linkage analysis was performed with short tandem repeat polymorphisms flanking these genes. Results. Affected family members had nyctalopia in the sixth decade of life and severe visual loss deve loped by the eighth decade. The donor retina showed marked loss of pho toreceptors except in the inferior periphery. A thick layer of extrace llular deposits was present between the RPE and Bruch's membrane in al l retinal regions. A 70-year-old affected family member had a retinopa thy resembling retinitis pigmentosa. Her 42-year-old daughter had a pa tch of punctate yellow-white lesions in one fundus and abnormal dark a daptation. The 50-year-old son of the donor had normal fundi but abnor mal dark adaptation and electroretinography No mutations were detected in the coding sequence of the rhodopsin, peripherin/RDS, and TIMP3 ge nes. Rhodopsin and TIMP3 were further excluded with linkage analysis. Conclusions. This novel retinal degeneration shares histopathologic an d clinical features with both Sorsby fundus dystrophy and retinitis pi gmentosa. The sub-RPE deposits may disrupt the exchange of nutrients a nd metabolites between the retina and the choriocapillaris, leading to photoreceptor dysfunction and degeneration.