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

IF 3.5 3区 医学 Q2 VIROLOGY
Viruses-Basel Pub Date : 2025-09-03 DOI:10.3390/v17091206
Jinxian Xu, Xinyan Zhang, Yi Liao, Ting Shi, Brendan Marshall, Ming Zhang
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Abstract

(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.

Abstract Image

Abstract Image

Abstract Image

Caspase-12缺失可减轻新生儿巨细胞病毒(MCMV)感染后老年BALB/c小鼠视网膜变性
(1)背景:老年BALB/c小鼠在新生儿全身性感染后,视网膜变性是由caspase-12激活引起的。(2)方法:对caspase-12-/-和caspase-12+/+小鼠(BALB/c背景下)腹腔注射MCMV或培养基(i.p),与年龄匹配的caspase-12-/-小鼠相比,MCMV潜伏感染的老年caspase-12-/-小鼠的平均视网膜厚度显著增加。虽然在感染caspase-12-/-和对照小鼠的眼睛中检测到相似水平的裂解caspase-1,但在感染caspase-12+/ -小鼠的眼睛中,活化的NF-κ b、裂解的caspase-8、MLKL、p-RIP3和p53的水平明显高于感染caspase-12-/-小鼠的眼睛。(4)结论:我们的研究结果表明,caspase-12通过凋亡和坏死下垂等多种途径参与MCMV眼潜伏期视网膜变性。
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来源期刊
Viruses-Basel
Viruses-Basel VIROLOGY-
CiteScore
7.30
自引率
12.80%
发文量
2445
审稿时长
1 months
期刊介绍: Viruses (ISSN 1999-4915) is an open access journal which provides an advanced forum for studies of viruses. It publishes reviews, regular research papers, communications, conference reports and short notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. We also encourage the publication of timely reviews and commentaries on topics of interest to the virology community and feature highlights from the virology literature in the ''News and Views'' section. Electronic files or software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.
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