Depletion of Caspase-12 Alleviates Retinal Degeneration in Aged BALB/c Mice Following Systemic Neonatal Infection by Murine Cytomegalovirus (MCMV).

(1)

Background

Retinal degeneration develops upon caspase-12 activation in aged BALB/c mice following systemic neonatal infection. (2)

Methods

MCMV or medium was injected intraperitoneally (i.p.) into caspase-12-/- and caspase-12+/+ mice (on BALB/c background) at <3 days after birth. At 8 and 12 months post infection (p.i.), eyes were analyzed by SD-OCT before eyes and extraocular tissues were collected and analyzed by plaque assay, H&E staining, TUNEL assay, Western blot and real-time RT-PCR. (3)

Results

Virus DNA, but not replicating virus, was present in eyes and extraocular tissues at 8 and 12 months p.i. Several MCMV genes were expressed in eyes of both MCMV-infected caspase-12-/- and caspase-12+/+ mice, while mean retinal thickness was significantly higher in MCMV latently infected aged caspase-12-/- mice compared to age-matched infected caspase-12+/+ mice. Although similar levels of cleaved caspase-1 were detected in eyes of both infected caspase-12-/- and control mice, significantly higher levels of activated NF-κB, cleaved caspase-8, MLKL, p-RIP3 and p53 were observed in eyes of infected caspase-12+/+ mice compared to eyes of infected caspase-12-/- mice. (4)

Conclusions

Our results suggest that caspase-12 contributes to retinal degeneration during MCMV ocular latency via multiple pathways including apoptosis and necroptosis.