RETINAL DEGENERATION IN THE PCD CEREBELLAR MUTANT MOUSE .2. ELECTRON-MICROSCOPIC ANALYSIS

The cerebellar ataxia in Purkinje cell degeneration (pcd) mutant mice results from the rapid loss of Purkinje cells between 3-5 wk after birth. The loss of photoreceptors in these mutants begins about the same time but proceeds slowly, with most photoreceptors being lost by 1 yr of age. Here, the retinas of pcd/pcd mice and their littermate controls from the age of 10 postnatal days to 15 mo. were analyzed by EM. The first signs of photoreceptor cell degeneration are apparent in the region of photoreceptor inner segments as early as postnatal day 13, and more prominentlty at day 18. During this time, the degeneration is characterized by a large number of vesicles, ranging in diameter from 150-350 nm, which are located in the extracellular space adjacent to the photoreceptor inner segments. Analysis of serial sections shows that most of these membrane-bound degeneration profiles are tubular in shape and some are continuous with the cell membrane of the inner segment. These profiles are thought to arise from tubular outpocketings of the inner segments which cleave off to form isolated membrane-bound profiles. This represents a new and unusual form of photoreceptor degeneraton. While the most obvious abnormality in the retina is degeneration of photoreceptor cells, Mueller cells also appear to be affected, with swollen apical processes often seen coursing through the outer nuclear layer.