Abstract
Purpose :
The relative roles of programmed cell death pathways toward retinal tissue destruction during the pathogenesis of AIDS-related cytomegalovirus retinitis remains largely unknown. We reported previously that necroptosis-associated molecule RIP1 (Receptor-Interacting Protein 1) mRNA is stimulated in MCMV-infected eyes and peaks at 6 days postinfection prior to development of MAIDS-related MCMV retinitis at day 10 postinfection when RIP1 mRNA production decreases [J Virol, 2012]. We therefore performed studies to test the hypothesis that RIP1 protein is detectable within retinal cells of eyes of MAIDS mice during development of MCMV retinitis and to determine the temporal pattern of RIP1 protein production relative to retinitis development.
Methods :
Eyes of groups of C57BL/6 mice with MAIDS were injected subretinally with MCMV or mock-infected (control). At 6 and 10 days postinfection, whole eyes were collected from all animals and sections of globes were subjected to immunostaining for detection and localization of RIP1 production.
Results :
When compared with mock-infected eyes, MCMV-infected eyes from MAIDS mice exhibited substantial positive immunostaining for RIP1 protein at day 6 postinfection. Numerous RIP1-positive cells were observed scattered throughout retinal tissues. In comparison, RIP1 protein detection was sharply diminished in MCMV-infected eye from MAIDS mice at day 10 postinfection at a time when retinal necrosis was observed.
Conclusions :
Immunostraining results confirmed that necroptosis-associated RIP1 protein is stimulated during progression of MAIDS-related MCMV retinitis. In agreement with RIP1 mRNA findings, RIP1 protein production was greatest at day 6 postinfection, but decreased considerably at day 10 postinfection during retinal necrosis. Our findings provide additional evidence that necroptosis operates during experimental MCMV retinitis pathogenesis in mice with retrovirus-induced immunosuppression and precedes retinitis development. The identification of RIP1-positive retinal cell types is currently under investigation.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.