Development and degeneration of retina in rds mutant mice: Electron microscopy

Abstract

In the retina of mice homozygous for the retinal degeneration slow (rds) gene, receptor outer segments failed to develop and typical disc structures were never observed. However, cilia surrounded by a plasma membrane were regularly present. At the time when outer segments grew in the normal retina, the optic ventricle in the mutant showed an accumulation of membrane-bound vesicles of varying size and density. The vesicles declined in frequency at later stages of degeneration. After initial growth, the inner segments in the mutant retina remained stunted but maintained their morphological differentiation, including the ciliary structures. Their number declined with loss of visual cells. In the mutant retina development of synapses, between the receptor cells and the processes of the horizontal cells and the bipolar cell dendrites, followed in normal sequence. Formation of spherule terminals of the rods, with one triad synapse, and of pedicle terminals of the cones, with multiple triad synapses, was recorded in the same way as in the normal retina. With loss of visual cells in the mutant retina, some of the profiles of the surviving spherule terminals showed an increased occurrence of two, three, or more synaptic sites. This growth resulted from enlargement and branching of the ribbons and sprouting from the postsynaptic elements. Similar changes were not observed in the pedicle terminals. The pigment epithelial cells in the mutant mice appeared initially normal, but phagolysosomal structures were absent. However, various inclusion bodies appeared within the pigment epithelial cells following degenerative changes in the retina. In some places, the basal infoldings deepened their furrows while thinning the cytoplasmic part of the epithelium. Failure to form the outer segments and the subsequent lysis of the visual cells appear to be the primary effects of the rds gene, whereas the synaptic growth in the sperule terminals and the changes in the pigment epithelium appear to be consequential to those defects.

Membrane curvature generation by a C-terminal amphipathic helix in peripherin-2/rds, a tetraspanin required for photoreceptor sensory cilium morphogenesis

“…Altogether, the results extend the notion that the E321L,K324A mutant is defective only in its ability to promote membrane fusion, and suggest the utility of this variant for examining the potential importance of fusogenic activity in vivo. P/rds function for curvature generation offers a direct explanation for the dysmorphic OS membrane phenotypes generated by protein loss in the retinal degeneration slow (rds) murine model (Jansen and Sanyal, 1984;Hawkins et al, 1985). A complete loss of curvature generating activity is predicted to totally disrupt disk morphogenesis and thereby prevent OS biogenesis -a phenotype consistent with that documented for the homozygous rds-null mouse (Jansen and Sanyal, 1984).…”

Proteolytic Shedding of the Extracellular Domain of Photoreceptor Cadherin

“…structural protein that resides at the OS disc rim and plays an essential role in disc morphogenesis (19,20). In the absence of RDS, the OS fails to form, and instead, large numbers of photoreceptor-derived membrane vesicles accumulate in the space between the photoreceptors and the RPE (21). Progressive photoreceptor degeneration occurs over the first several months of life.…”

“…A nearly identical immunostaining pattern is seen with the anti-N-terminal prCAD antibody. The pattern of prCAD localization corresponds to the extracellular vesicles that accumulate in rds(Ϫ/Ϫ) retinas (21). Interestingly, in rds(Ϫ/Ϫ) photoreceptors, RP1 remains localized to discrete structures; these presumably correspond to the truncated axoneme or the connecting cilium (Fig.…”

Loss of the Cholesterol-Binding Protein Prominin-1/CD133 Causes Disk Dysmorphogenesis and Photoreceptor Degeneration

“…؊/؊ mice Since impaired OS morphogenesis, in combination with ectopic distribution of visual pigment, may lead to photoreceptor degeneration (Jansen and Sanyal, 1984;Bascom et al, 1992), we studied, by TUNEL staining, whether loss of Prom-1 induced excessive retinal cell apoptosis. No genotypic differences were observed in retinal cell apoptosis in the INL and ONL at P10 (n ϭ 6, p ϭ NS) (Fig.…”