Abstract
Purpose :
We have been investigating the potential roles of several cell death pathways in the pathophysiology of AIDS-related human cytomegalovirus retinitis using a mouse model of MCMV retinitis in mice with MAIDS. Autophagy is a protective form of cell death induced during periods of stress. Previous work by others has shown autophagy to play an important role in the homeostasis of RPE, but MCMV may possess a mechanism during active replication to inhibit a late stage of autophagy in RPE. Because beclin-1 has a central role in autophagy, we tested the hypothesis that beclin-1, as a marker for autophagy, is downregulated during onset and development of MAIDS-related MCMV retinitis.
Methods :
We have shown previously that mice with MAIDS of 4-weeks duration are resistant to MCMV retinitis, but mice with MAIDS of 10 weeks duration are susceptible to MCMV retinitis. The left eyes of groups of C57BL/6 mice with MAIDS-4 or MAIDS-10 were injected subretinally with MCMV. Right eyes were injected with maintenance medium only (control). At 3, 6, and 10 days postinfection, all eyes were collected and subjected to RT-PCR assay for detection and quantification of beclin-1 mRNA.
Results :
Beclin-1 mRNA was detected but not stimulated nor downregulated within MCMV-infected eyes of MAIDS-4 mice resistant to retinitis at 3, 6, and 10 days postinfection. Similarly, MCMV-infected eyes of MAIDS-10 mice susceptible to retinitis showed detectable beclin-1 mRNA but without stimulation nor downregulation at all days postinfection investigated, even at 10 days postinfection at time of retinitis development.
Conclusions :
MCMV infection of eyes of retinitis-resistant MAIDS-4 mice as well as retinitis-susceptible MAIDS-10 mice showed neither stimulation nor downregulation of beclin-1 mRNA. These preliminary findings suggest that autophagy may not play a prominent role in the development of MAIDS-related MCMV retinitis. Future studies will investigate the fate of other autophagy-related molecules during development of MCMV retinitis in mice with MAIDS. It has not escaped our attention that caspase-mediated cleavage of beclin-1 promotes crosstalk between apoptosis and autophagy.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.