Abstract
Abstract: :
Purpose: To search for histopathologic–genotype correlations in human retinal degenerations by performing a meta–analysis of published cases. Methods: We reviewed published histopathologic findings of eyes from patients with retinitis pigmentosa or an allied disease for whom the responsible gene was identified in the patient or an affected relative. In some cases, the published findings predated the gene identification by many years. We created a database of the diagnosis, major histopathologic findings, and responsible mutations. Results: A total of 21 cases were found dating from 1974 to 2003. Eleven had retinitis pigmentosa (RP): 9 had autosomal dominant RP (including 6 different RHO mutations and 1 PRPC8 mutation), 0 had recessive RP, and 2 had X–linked RP (different RPGR mutations). We found 3 cases of dominant spinocerebellar ataxia (SCA7), 2 of Leber’s congenital amaurosis (LCA) (AIPL1 and RPE65), and one each of dominant cone degeneration (GCAP1), X–linked cone degeneration (RCP), enhanced S–cone syndrome (NR2E3), late–onset retinal degeneration (CTRP5), and hypobetalipoproteinemia (APOB). All cases had histopathologic evidence of a reduction in photoreceptor number except one case who died of SCA7 disease. Better preservation of cones vs. rods were described in cases with mutations in RHO, PRPC8, RPGR, and NR2E3. Relative sparing of photoreceptors in the central retina or the far periphery was found in RHO, SCA7, NR2E3, RCP, RPGR and AIPL1. Outer segment and/or inner segment abnormalities were frequent, being found in RHO, PRPC8, SCA7, GCAP1, NR2E3, RCP, RPGR, and APOB. Inclusion bodies and/or perinuclear cytoplasmic membranous swirls were found in cases with mutations in RHO, PRPC8, and SCA7. RPE abnormalities were present in all cases except 2 with RHO mutations and 1 with SCA7 mutation. Hypertrophied Müller processes were described in RHO, NR2E3, RPGR, and CTRP5. Sub or pre–RPE deposits were reported in CTRP5, SCA7 and APOB. In 1 RHO case there was a description of neurite sprouting from remaining peripheral rods and cones. Conclusions: There is a range of photoreceptor and RPE abnormalities evident, sometimes even among cases with mutations in the same gene. The limited numbers of cases appear to hamper any specific histopathologic–genotype correlations. Our database should serve as a starting point for a future, larger collection of such cases.
Keywords: retinal degenerations: hereditary • retina • pathology: human