Genetic interaction in the retinal degeneration of mice

In the retina of mice, homozygous for the rd (retinal degeneration) gene, rapid loss of visual cells starting from around 10 days after birth reduces the outernuclear layer to a single row at the age of 21 days. In the mouse, homozygous for the rds (retinal degeneration slow) gene, the retina fails to develop the receptor outer segments and lacks rhodopsin, and a very slow loss of visual cells starting from two weeks after birth results in progressive reduction of the outer nuclear layer. In order to examine the influence of absence of rhodopsin on the degeneration caused by the rd gene, mice homozygous for both the rd and the rds genes were produced by appropriate breeding. In the double homozygous mutants, the visual cells remain lacking in receptor outer segments, but ultrastructural changes in the inner segments and visual cell death as indicated by the appearance of pycnotic nuclei start at the same time as in the rd genotype. However, the rate of degeneration is considerably slowed down in the double homozygotes and the thickness of the outer nuclear layer at 14, 21 and 28 days remains consistently thicker than in the retina of rd mice. A single row of outer nuclei, as seen in the rd retina at 21 days, is seen in the double homozygotes at 2 months. The relevance of the present findings in relation to the therapeutic use of vitamin A in retinitis pigmentosa is discussed.