Development and degeneration of retina in rds mutant mice: light and electron microscopic observations in...

Mice, homozygous for the rds gene, fail to develop the receptor outer segments and show a slow reduction of the outer nuclear layer. A series of 13 chimaeric mice was produced by combining morulae from albino rds/rds and pigmented normal (+/+) mice. At 3-4 weeks, variable stretches of visual cells without outer segments were observed together with stretches of visual cells with normal outer segments. The location of these areas was unrelated to the genotype of the overlying pigment epithelium. Phagosomes containing outer segment debris were present in albino pigment epithelial cells, located over normal outer segments, indicating normal functional properties of rds/rds pigment epithelial cells. At 9 months, regions with visual cell loss were observed underlying both types of pigment epithelial cells. Regions showing normal and intermediate thicknesses of the outer nuclear layer were seen more often than regions showing rds/rds type distribution. In another series of eight chimaeras, consisting of albino rds/rds and pigmented rd/rd genotypes, the eyes examined at 22 days showed more pronounced visual cell loss than in the rds----normal retinas at 9 months. Regions of the outer nuclear layer, containing a single row of cone perikarya, were similar to the rd/rd phenotype and differed from the phenotype of the double homozygous rd/rd rds/rds retina, which has a slower rate of degeneration than in rd/rd mice. Visual cell loss in these chimaeras at 9 months was similar to that in the rds/rds retina of the same age. The findings show that the expression of the rds gene, resulting in failure of outer segment development and eventual death of visual cells is unrelated to the genotype of the overlying pigment epithelial cells and suggest that the gene acts within the neural retina and possibly intracellularly in the visual cells.