PIGMENT EPITHELIAL AND RETINAL PHENOTYPES MI(VIT), MUTANT MOUSE

Citation
Rl. Sidman et al., PIGMENT EPITHELIAL AND RETINAL PHENOTYPES MI(VIT), MUTANT MOUSE, Investigative ophthalmology & visual science, 37(6), 1996, pp. 1097-1115
Citations number
61
Categorie Soggetti
Ophthalmology
ISSN journal
01460404
Volume
37
Issue
6
Year of publication
1996
Pages
1097 - 1115
Database
ISI
SICI code
0146-0404(1996)37:6<1097:PEARPM>2.0.ZU;2-H
Abstract
Purpose. To describe the abnormal phenotype in retinal pigment epithel ium (RPE) and neural retina of vitiligo mutant mice from embryonic sta ges to old age. Methods. Eyes of wild-type controls and congenic vitil igo mutants were examined by light and electron microscopy from embryo nic day (E) 12 to 2 years of age. The amount and distribution of pigme nt in the RPE was studied in wholemounts. Results. Earliest phenotypic expression of mi(vit) is seen in the RPE, which is abnormally multila yered dorsally at E12 to E13, and contains both hyperpigmented and hyp opigmented patches. Postnatally, most RPE cells have abnormally short, compact, apical microvilli not containing melanosomes and not interdi gitating with rod outer segments (ROS). Rod outer segments begin to de generate relatively late, at approximately postnatal day (P) 30, and f ragments accumulate in the subretinal space; photoreceptor nuclei decr ease in number progressively from approximately P60 to P500. Retinal d etachment, more prominent than in most other retinal degenerations, be gins as ROS break up. Additional unusual events are the appearance of macrophage-like cells in the subretinal space by P21 to P60 and extens ive shedding of photoreceptor nuclei across the external limiting memb rane and into the subretinal space from approximately P180 to P500. Ph otoreceptor cell degeneration follows a radial gradient, more severe c entrally, and is more advanced superiorly than inferiorly. By 2 years, almost all rod and cone cells are gone, and the residual neural retin a is invaded by heavily pigmented cells. Conclusions. The initial ocul ar target of the mi(vit) gene is the RPE, which is abnormal for many w eeks before photoreceptor cells differentiate and become demonstrably affected. The authors hypothesize that the slowly progressive photorec eptor cell degeneration is secondary to abnormal function of the RPE. This mutation serves to refocus attention on critical influences of th e RPE on function and maintenance of photoreceptor cells.