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Xinyan Zhang, Jinxian Xu, Brendan Marshall, Ming Zhang; Role of caspase 12 in death of uninfected retinal cells during murine cytomegalovirus (MCMV) retinitis. Invest. Ophthalmol. Vis. Sci. 2020;61(7):435.
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© ARVO (1962-2015); The Authors (2016-present)
Death of uninfected bystander neuronal cells is an important component of the pathogenesis of CMV retinitis. Our previous results have shown that caspase 3–dependent and –independent pathways are involved in death of uninfected bystander cells during murine MCMV retinitis and caspase-12, which is mainly located on the cytoplasmic side of the endoplasmic reticulum (ER), is up-regulated during this process. The purpose of this study was to determine if caspase 12 plays a significant role in death of uninfected retinal cells by comparing cell death in caspase 12-depleted mice (caspase-12-/-) and caspase-12+/+ control BALB/c mice.
Caspase-12-/- mice, or caspase-12+/+ mice were immunosuppressed with methylprednisolone and infected with 5×103 plaque-forming units (PFU) of the K181 strain of MCMV or mock control via the supraciliary route. Injected eyes were analyzed by plaque assay, hematoxylin and eosin (H&E) staining, TUNEL assay, Western blot, as well as immunohistochemical staining.
Significant more cleaved caspase 12 was detected in MCMV infected caspase-12+/+ eyes than in uninfected controls eyes. Similar amount of virus was recovered from MCMV injected eyes of immunosuppressed caspase-12-/- mice and caspase-12+/+ mice. Significant low levels of cleaved caspase-3 or cleaved PARP were detected in the injected eyes of caspase-12-/- mice than in the injected eyes of caspase-12+/+ mice. In addition, the protein levels of PUMA, a proapoptotic BH3-only Bcl-2 family member and critical mediator of cell death via mitochondrial pathway, were significantly lower in the injected eyes of caspase-12-/- mice than in the injected eyes of caspase-12+/+ mice.
During MCMV retinitis, caspase 12 is activated and has an important role in death of uninfected bystander retinal cells through caspase 3–dependent apoptosis.
This is a 2020 ARVO Annual Meeting abstract.
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