Sub-retinal pigment epithelial deposits in a dominant late-onset retinal degeneration.
OBJECTIVE
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.
Kuntz
C A
CA
Department of Ophthalmology, University of Washington, Seattle 98195-6485, USA.
Jacobson
S G
SG
Cideciyan
A V
AV
Li
Z Y
ZY
Stone
E M
EM
Possin
D
D
Milam
A H
AH
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D003315:Cornea / Q000473:pathology; D004247:DNA / Q000097:blood; D004596:Electroretinography; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D010375:Pedigree; D010857:Pigment Epithelium of Eye / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D014792:Visual Acuity
D004247:DNA