The mechanisms that contribute to
retinal tissue destruction during the onset and progression of
AIDS-related human cytomegalovirus (HCMV)
retinitis remain unclear. Evidence for the stimulation of multiple cell death pathways including apoptosis, necroptosis, and pyroptosis during the pathogenesis of experimental murine cytomegalovirus (MCMV)
retinitis in mice with retrovirus-induced immunosuppression (
MAIDS) has been reported. Parthanatos is a
caspase-independent cell death pathway mediated by rapid overactivation of
poly (ADP-ribose) polymerase-1 (PARP-1) and distinct from other cell death pathways. Using the
MAIDS model of MCMV
retinitis, studies were performed to test the hypothesis that intraocular MCMV
infection of mice with
MAIDS stimulates parthanatos-associated messenger RNAs (mRNAs) and
proteins within the eye during the development of
retinal necrosis that takes place by 10 days after MCMV
infection. MCMV-infected eyes of
MAIDS mice exhibited significant stimulation of PARP-1
mRNA and
proteins at 3 days after
infection but declined thereafter at 6 and 10 days after
infection. Additional studies showed the intraocular stimulation of mRNAs or
proteins before MCMV
retinitis development for two additional participants in parthanatos,
polymer of
ADP-ribose and
poly (ADP-ribose) glycohydrolase. These results provide new evidence for a role for parthanatos during
MAIDS-related MCMV
retinitis that may also extend to
AIDS-related HCMV
retinitis.