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Morphological characterization of the retinal degeneration in three strains of mice carrying the rd-3 mutation

Published online by Cambridge University Press:  13 February 2006

KENNETH A. LINBERG ,
ROBERT N. FARISS ,
JOHN R. HECKENLIVELY ,
DEBORA B. FARBER  and
STEVEN K. FISHER
KENNETH A. LINBERG
Affiliation:
Neuroscience Research Institute, University of California, Santa Barbara, California
ROBERT N. FARISS
Affiliation:
Neuroscience Research Institute, University of California, Santa Barbara, California Current Address of Robert N. Fariss: Biological Imaging Core, NEI-NIH, Bethesda, MD 20892-0703, USA
JOHN R. HECKENLIVELY
Affiliation:
The Jules Stein Eye Institute, Los Angeles, California Harbor-UCLA Medical Center, Torrance, California Current Address of John R. Heckenlively: Ophthalmology, University of Michigan, Ann Arbor, MI 48105, USA
DEBORA B. FARBER
Affiliation:
The Jules Stein Eye Institute, Los Angeles, California The Molecular Biology Institute, UCLA, Los Angeles, California
STEVEN K. FISHER
Affiliation:
Neuroscience Research Institute, University of California, Santa Barbara, California Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, California
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Abstract

Retinal development in 3 strains of rd-3/rd-3 mutant mice, previously shown to have different rates of degeneration, was studied using light, electron, and immunofluorescence microscopy. The time course and phenotype of the degeneration as well as details on the mechanism of massive photoreceptor cell loss are compared with other known retinal degenerations in mice. Up until postnatal day (P) 10, the retinas of all three strains (RBF, 4Bnr, In-30) develop similarly to those of pigmented and nonpigmented controls. TUNEL-positive cells appear in the outer nuclear layer (ONL) by P14, and reach a maximum in all three mutant strains around P21. Scattered rods and cones form a loose, monolayered ONL by 8 weeks in the albino RBF strain, by 10 weeks in the albino 4Bnr strain, and by 16 weeks in the pigmented In-30 strain. Though the initial degeneration begins in the central retina, there is no preferred gradient of cell death between central and peripheral photoreceptors. Rods and cones are present at all ages examined. During development, stacks of outer segments (OS) form in all three strains though they never achieve full adult lengths, and often have disorganized, atypical OS. Rod opsin is expressed in the developing OS but is redistributed into plasma membrane as OS degeneration proceeds. Retinal pigment epithelial (RPE) cells of all mutant strains contain packets of phagocytosed OS, and their apical processes associate with the distal ends of the OS. At their synaptic sites, photoreceptor terminals contain ribbons apposed to apparently normal postsynaptic triads. As photoreceptors are lost, Müller cells fill in space in the ONL but they do not appear to undergo significant hypertrophy or migration, though during the degeneration, glial fibrillary acidic protein (GFAP) expression is gradually upregulated. Macrophage-like cells are found frequently in the subretinal space after the onset of photoreceptor apoptosis. As OS disappear, the RPE apical processes revert to simple microvilli. Late in the degeneration, some RPE cells die and neighboring cells appear to flatten as if to maintain confluence. In regions of RPE cell loss that happen to lie above retina where the ONL is gone, cells of the inner nuclear layer (INL), wrapped by Müller cell processes, may front directly on Bruch's membrane.

Keywords

Inherited retinal degenerationApoptosisPhotoreceptors
Type
Research Article
Information
Visual Neuroscience , Volume 22 , Issue 6 , November 2005 , pp. 721 - 734
Copyright
© 2005 Cambridge University Press

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