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

被引:233
作者
Cideciyan, AV [1 ]
Hood, DC
Huang, YJ
Banin, E
Li, ZY
Stone, EM
Milam, AH
Jacobson, SG
机构
[1] Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Philadelphia, PA 19104 USA
[2] Columbia Univ, Dept Psychol, New York, NY 10027 USA
[3] Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA
[4] Univ Iowa, Dept Ophthalmol, Iowa City, IA 52242 USA
关键词
D O I
10.1073/pnas.95.12.7103
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 tan be relatively innocuous and epigenetic factors may play a major role in the retinal degeneration.
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收藏
页码:7103 / 7108
页数:6
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