Inflammatory response and retinal ganglion cell degeneration following intraocular injection of ME7.
Scrapie is a prion disease which occurs naturally in sheep and which can be transmitted experimentally to rodents. After intracerebral injection of ME7 into mouse, an atypical inflammatory response, characterized by T-lymphocytes and activated microglia is present early in the course of the disease. In the present work, we have investigated the relationship between this inflammatory response, astrocytosis and neuronal loss along the visual pathway after intraocular injection (intraocular) of ME7 in C57BL/6J mice. We have demonstrated that microglia activation and T-lymphocyte recruitment accompanies the spread of prion pathology along the visual pathway and in the early stages of the disease is restricted to the subcortical visual pathway. Inflammation was also present in non-visual areas in association with PrPsc deposition at late stages of the disease, possibily indicating that diffusion of the scrapie agent also contributes to the spread of the disease. After intraocular injection of the prion agent, the disease is believed to be transported into the brain via axons of retinal ganglion cells (RGCs). Despite the high levels of infectivity reported to be present in the retina early in the disease after intraocular injection of ME7, retinal pathology has not been extensively investigated. We have studied the RGCs response in whole mount retinas after intraocular injection of ME7. We have shown that RGCs degenerate after intraocular injection of ME7 whereas amacrine cells, retinal interneurones, are more resistant. Our results suggest that two distinct population of neurones, exposed in vivo at the same time to the same agent scrapie strain, show different susceptibility to the toxic effects of PrPsc.
Russelakis-Carneiro
M
M
Departamento de Fisiologia, Universidade Federal do Pará, Belém, Pará, Brazil.
Betmouni
S
S
Perry
V H
VH
D000818:Animals; D002452:Cell Count; D005123:Eye; D005260:Female; D007267:Injections; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011328:Prions; D012160:Retina / Q000473:pathology; D012162:Retinal Degeneration / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000473:pathology*; D012608:Scrapie / Q000473:pathology*; D016019:Survival Analysis; D013997:Time Factors
D011328:Prions