Investigative Ophthalmology & Visual Science, Vol 37, 1772-1782, Copyright © 1996 by Association for Research in Vision and Ophthalmology

ARTICLES AND REPORTS

Sub-retinal pigment epithelial deposits in a dominant late-onset retinal degeneration

CA Kuntz, SG Jacobson, AV Cideciyan, ZY Li, EM Stone, D Possin and AH Milam
Department of Ophthalmology, University of Washington, Seattle 98195- 6485, USA.

PURPOSE. To determine the pathogenesis of an autosomal dominant late- onset retinal degeneration by studies of the retinal histopathology, phenotype of family members, and candidate genes for the disease. METHODS. The retina from an 80-year-old patient donor was prepared for light and electron microscopy, including special stains and immunocytochemistry. Family members were examined clinically and with retinal function 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 developed by the eighth decade. The donor retina showed marked loss of photoreceptors except in the inferior periphery. A thick layer of extracellular deposits was present between the RPE and Bruch's membrane in all retinal regions. A 70-year-old affected family member had a retinopathy resembling retinitis pigmentosa. Her 42-year-old daughter had a patch of punctate yellow-white lesions in one fundus and abnormal dark adaptation. The 50-year-old son of the donor had normal fundi but abnormal dark adaptation and electroretinography. No mutations were detected in the coding sequence of the rhodopsin, peripherin/RDS, and TIMP3 genes. Rhodopsin and TIMP3 were further excluded with linkage analysis. CONCLUSIONS. This novel retinal degeneration shares histopathologic and clinical features with both Sorsby fundus dystrophy and retinitis pigmentosa. The sub-RPE deposits may disrupt the exchange of nutrients and metabolites between the retina and the choriocapillaris, leading to photoreceptor dysfunction and degeneration.

This article has been cited by other articles:

				X. Shu, B. Tulloch, A. Lennon, D. Vlachantoni, X. Zhou, C. Hayward, and A. F. Wright Disease mechanisms in late-onset retinal macular degeneration associated with mutation in C1QTNF5 Hum. Mol. Genet., May 15, 2006; 15(10): 1680 - 1689. [Abstract] [Full Text] [PDF]

				R. Ayyagari, M. N. A. Mandal, A. J. Karoukis, L. Chen, N. C. McLaren, M. Lichter, D. T. Wong, P. F. Hitchcock, R. C. Caruso, S. E. Moroi, et al. Late-Onset Macular Degeneration and Long Anterior Lens Zonules Result from a CTRP5 Gene Mutation Invest. Ophthalmol. Vis. Sci., September 1, 2005; 46(9): 3363 - 3371. [Abstract] [Full Text] [PDF]

				S. Amin, N. H. V. Chong, T. A. Bailey, J. Zhang, C. Knupp, M. E. Cheetham, J. Greenwood, and P. J. Luthert Modulation of Sub-RPE Deposits In Vitro: A Potential Model for Age-Related Macular Degeneration Invest. Ophthalmol. Vis. Sci., May 1, 2004; 45(5): 1281 - 1288. [Abstract] [Full Text] [PDF]

				M. A. Zarbin Current Concepts in the Pathogenesis of Age-Related Macular Degeneration Arch Ophthalmol, April 1, 2004; 122(4): 598 - 614. [Abstract] [Full Text] [PDF]

				C. Hayward, X. Shu, A. V. Cideciyan, A. Lennon, P. Barran, S. Zareparsi, L. Sawyer, G. Hendry, B. Dhillon, A. H. Milam, et al. Mutation in a short-chain collagen gene, CTRP5, results in extracellular deposit formation in late-onset retinal degeneration: a genetic model for age-related macular degeneration Hum. Mol. Genet., October 16, 2003; 12(20): 2657 - 2667. [Abstract] [Full Text] [PDF]

				S. G. Jacobson, A. V. Cideciyan, E. Wright, and A. F. Wright Phenotypic Marker for Early Disease Detection in Dominant Late-Onset Retinal Degeneration Invest. Ophthalmol. Vis. Sci., July 1, 2001; 42(8): 1882 - 1890. [Abstract] [Full Text] [PDF]

				C. A. Curcio, C. Owsley, and G. R. Jackson Spare the Rods, Save the Cones in Aging and Age-related Maculopathy Invest. Ophthalmol. Vis. Sci., July 1, 2000; 41(8): 2015 - 2018. [Full Text]

				N. H. V. Chong, R. A. Alexander, T. Gin, A. C. Bird, and P. J. Luthert TIMP-3, Collagen, and Elastin Immunohistochemistry and Histopathology of Sorsby’s Fundus Dystrophy Invest. Ophthalmol. Vis. Sci., March 1, 2000; 41(3): 898 - 902. [Abstract] [Full Text]

				R. N Fariss, S. S Apte, P. J Luthert, A. C Bird, and A. H Milam Accumulation of tissue inhibitor of metalloproteinases-3 in human eyes with Sorsby's fundus dystrophy or retinitis pigmentosa Br. J. Ophthalmol., November 1, 1998; 82(11): 1329 - 1334. [Abstract] [Full Text]