Disease sequence from mutant rhodopsin allele to rod and cone photoreceptor degeneration in man

Artur V Cideciyan; Donald C Hood; Yijun Huang; Eyal Banin; Zong-Yi Li; Edwin M Stone; Ann H Milam; Samuel G Jacobson

doi:10.1073/pnas.95.12.7103

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Disease sequence from mutant rhodopsin allele to rod and cone photoreceptor degeneration in man

Journal article

Open access

Peer reviewed

Disease sequence from mutant rhodopsin allele to rod and cone photoreceptor degeneration in man

Artur V Cideciyan, Donald C Hood, Yijun Huang, Eyal Banin, Zong-Yi Li, Edwin M Stone, Ann H Milam and Samuel G Jacobson

Proceedings of the National Academy of Sciences - PNAS, Vol.95(12), pp.7103-7108

06/09/1998

DOI: 10.1073/pnas.95.12.7103

PMID: 9618546

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Abstract

Mutations in the gene encoding rhodopsin, the visual pigment in rod photoreceptors, lead to retinal degeneration in species from Drosophila to man. The pathogenic sequence from rod cell-specific mutation to degeneration of rods and cones remains unclear. To understand the disease process in man, we studied heterozygotes with 18 different rhodopsin gene mutations by using noninvasive tests of rod and cone function and retinal histopathology. Two classes of disease expression were found, and there was allele-specificity. Class A mutants lead to severely abnormal rod function across the retina early in life; topography of residual cone function parallels cone cell density. Class B mutants are compatible with normal rods in adult life in some retinal regions or throughout the retina, and there is a slow stereotypical disease sequence. Disease manifests as a loss of rod photoreceptor outer segments, not singly but in microscopic patches that coalesce into larger irregular areas of degeneration. Cone outer segment function remains normal until >75% of rod outer segments are lost. The topography of cone loss coincides with that of rod loss. Most class B mutants show an inferior-nasal to superior-temporal retinal gradient of disease vulnerability associated with visual cycle abnormalities. Class A mutant alleles behave as if cytotoxic; class B mutants can be relatively innocuous and epigenetic factors may play a major role in the retinal degeneration.

Mutation

Rhodopsin - genetics

Retinal Degeneration - genetics

Humans

Alleles

Adult

Retinal Degeneration - physiopathology

Retinal Cone Photoreceptor Cells - physiopathology

Retinal Rod Photoreceptor Cells - physiopathology

Details

Title: Subtitle: Disease sequence from mutant rhodopsin allele to rod and cone photoreceptor degeneration in man
Creators: Artur V Cideciyan - Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USA. cideciya@mail.med.upenn.edu
Donald C Hood
Yijun Huang
Eyal Banin
Zong-Yi Li
Edwin M Stone
Ann H Milam
Samuel G Jacobson
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.95(12), pp.7103-7108
DOI: 10.1073/pnas.95.12.7103
PMID: 9618546
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: United States
Grant note: EY-01730 / NEI NIH HHS EY-01311 / NEI NIH HHS EY-05627 / NEI NIH HHS
Language: English
Date published: 06/09/1998
Academic Unit: Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9983979937102771

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