C57BL 6J- vit vit mouse model of retinal degeneration: Light microscopic analysis and evaluation of rhodopsin levels

The C57BL 6J- vit vit mouse is a newly described model of retinal degeneration in which photoreceptor cells die over the course of a year and the retinal pigment epithelium is unevenly pigmented. The present study utilized histological and biochemical techniques to assess the progression of the retinal degeneration in the vit vit mouse ages 2 weeks to 8 months. Results of systematic morphometric evaluation indicated that the inner nuclear and plexiform layers of the retina are similar in thickness to age-matched C57BL 6J controls, but the outer plexiform layer is significantly thinner by 4 months. Rows of photoreceptor cells are lost at a rate of about one per month beginning at 2 months of age. By 8 months, the photoreceptor cell nuclei have diminished to only two to three rows. Inner segments of the vit vit retina are similar in length to controls. Outer segments separate from the RPE during the first 2 months, they seem to be elongated at 2-3 months, but become severely disrupted past 4 months. Beginning at about 5 months, numerous darkly-staining cells resembling photoreceptor cell nuclei are observed in the area of the inner and outer segments and the subretinal space. Spectrophotometric analysis of rhodopsin indicated similar levels in vit vit and controls at 6 weeks but a 50% reduction by 22 weeks. At 46 weeks, the level of rhodopsin in the mutant animal was less than 0·1 nmol per retina. The loss of rhodopsin in the vit vit retinas correlated strongly with the decreasing number of rows of photoreceptor cells. The degenerative changes observed in the vit vit mouse are compared to those in other rodent models of inherited retinal degeneration and the potential usefulness of the vit vit mouse as a model for human retinitis pigmentosa is discussed.