Photoreceptor degeneration preceding clinical scrapie encephalopathy in hamsters.

Hamsters experimentally inoculated with scrapie had histologic and ultrastructural changes in their retinas before clinical signs of central nervous system disease became evident at 50 days postinoculation. The retinal changes were limited to the photoreceptors and began with degenerative changes in the inner segments as early as 8 days postinoculation. As the inner segment lesions became more prominent, associated degenerative changes within outer segments were seen (38 days postinoculation). An influx of macrophages was associated with increasing degenerative changes; these cells engulfed cellular debris did not appear to contribute directly to the degenerative process. Retinas having the greatest damage to the inner segment area also had moderate reduction in outer nuclear layer density and outer segment length, and in numbers of outer segments. All of the retinal changes described occurred almost exclusively in the central to mid-region of retina with relative sparing of peripheral retina.

Retinal degeneration during clinical scrapie encephalopathy in hamsters.

Weanling hamsters were inoculated intracerebrally with brain suspensions from normal or scrapie-infected hamsters. A third group of uninoculated animal was fed cuprizone. Histologic and electron microscopic examination of the neural retinas and retinal pigment epithelium was done. At 50 days postinoculation, when scrapie-infected animals began to show clinical signs of encephalopathy, there was a variable degree of photoreceptor degeneration. By the time animals were moribund, at 74 days postinoculation, photoreceptor degeneration was severe, as demonstrated by loss of most outer and inner segments and cell bodies. The outer plexiform, inner nuclear, and inner plexiform layers were reduced in thickness. Some retinal pigment epithelial cells contained lipoidal inclusions. The neural retinas and retinal pigment epithelium of noninfected and cuprizone-treated animals were normal. We have previously shown that the scrapie agent accumulates in the retina; that together with our present work, we conclude that the scrapie agent is the cause of photoreceptor degeneration in experimentally inoculated hamsters.

Histology and fine structure of the hamster retinal pigment epithelium.

The retinal pigment epithelium of normal adult golden Syrian hamsters was examined by light and electron microscopy, using conventional and enzyme histochemical techniques. Hamster retinal pigment epithelium was composed of a single layer of cuboidal cells that had marked infolding of the basal cell wall and numerous microvillous processes extending from the apical surface. Melanin content varied within each specimen and there appeared to be incomplete or aberrant development of many melanin granules. Many incompletely melanized granules showed acid phosphate activity. There were the usual cell organelles, and Golgi complexes. Large phagosomes increased in number in the morning hours. Autophagic vacuoles and small lipid droplets were commonly seen. Occasional basal bodies, cilia, and root filaments were found. In two specimens, a curious intranuclear paracrystalline structure was observed.

Retinal degeneration in experimental scrapie after intraperitoneal or subcutaneous inoculation of hamsters.

Hamsters injected intraperitoneally or subcutaneously with the scrapie agent developed photoreceptor degeneration. The degree of degeneration did not correlate well with infectivity titers of retinal tissue or stage of clinical encephalopathy, and was not as great as seen in intracerebrally injected animals. We conclude that retinal degeneration is universal in hamsters experimentally inoculated with the scrapie agent regardless of the route of inoculation.

Asymmetry of retinal lesions in experimental scrapie after intracerebral inoculation of hamsters.

Hamsters injected into the right cerebral hemisphere with the scrapie agent developed retinal lesions to a greater extent in the contralateral than in the ipsilateral eye. This asymmetry was evident during the incubation period as well as during the clinical encephalopathy. The results explain much of the variation in the degree of retinal disease seen earlier at specific times after inoculation. Moreover, they strengthen the hypothesis that scrapie spreads via neurons.

Photoreceptor degeneration during infection with various strains of the scrapie agent in hamsters.

Hamsters were inoculated intracerebrally with the 22C, 79A, and ME7 strains of the scrapie agent to compare the effects on the retina with those caused by strain 263K. The animals developed clinical signs of encephalopathy. Photoreceptor degeneration occurred in all experimental animals. The changes were similar to those seen in animals infected with the 263K strain of scrapie although somewhat more variable and less extensive.

Photoreceptor degeneration in experimental transmissible mink encephalopathy of hamsters.

Hamsters were inoculated intracerebrally with the agent of transmissible mink encephalopathy and developed clerical signs of encephalopathy. Photoreceptor degeneration occurred in all animals examined histologically. The changes were similar to those in scrapie, although less extensive. The findings suggest that either transmissible mink encephalopathy is a mink-adapted form of scrapie or, in rodents, photoreceptor degeneration is a characteristic of infection with agents of the spongiform encephalopathies.

Neural pathogenesis of experimental scrapie after intraocular inoculation of hamsters.

Hamsters were inoculated intravitreally with the scrapie agent. All animals developed scrapie and retinal degeneration typical of scrapie. The retinal degeneration was greater in the inoculated eyes than in the uninoculated eyes. Replication of the scrapie agent was rapid in the inoculated eye. Infectivity then spread slowly down the ipsilateral optic nerve to the brain. The replication in the brain paralleled that in the retina of the uninoculated eye. The results support a neural spread of scrapie.