Retinal degeneration in the pcd/pcd mutant mouse: accumulation of spherules in the interphotoreceptor space.

The Purkinje cell degeneration (pcd) mutant mouse rapidly loses cerebellar Purkinje cells and about 50% of its retinal photoreceptor cells at between 3 and 5 weeks of age, and thereafter slowly loses the remaining photoreceptor cells during the first year of life. An ultrastructural study of the developing photoreceptor cells of the pcd/pcd retina was undertaken using both transmission and scanning electron microscopy to characterize further the previously reported retinal vesicles associated with this mutation. Transmission electron microscopy (TEM) revealed an abundance of 'bead-like' vesicles or excrescences in the extracellular matrix surrounding the inner segment region at post-natal day (P) 25. The vesicles are membrane bound, amorphous in appearance and vary in size from 125 to 370 nm. Scanning electron microscopy suggests that the vesicles seen with TEM are actually spherules formed from outpocketing and pinching off of the plasma membrane in the mitochondria-rich region of the rod inner segment. At P25, the spherules are concentrated in the interphotoreceptor space at the level of rod inner segments; at P40, however, they are displaced from their origin and appear mostly at the level of rod outer segments and in the subretinal space.