PMID- 36901754 OWN - NLM STAT- MEDLINE DCOM- 20230314 LR - 20240109 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 5 DP - 2023 Feb 21 TI - Transcriptome Analysis of Retinal and Choroidal Pathologies in Aged BALB/c Mice Following Systemic Neonatal Murine Cytomegalovirus Infection. LID - 10.3390/ijms24054322 [doi] LID - 4322 AB - Our previous studies have shown that systemic neonatal murine cytomegalovirus (MCMV) infection of BALB/c mice spread to the eye with subsequent establishment of latency in choroid/RPE. In this study, RNA sequencing (RNA-Seq) analysis was used to determine the molecular genetic changes and pathways affected by ocular MCMV latency. MCMV (50 pfu per mouse) or medium as control were injected intra-peritoneally (i.p.) into BALB/c mice at <3 days after birth. At 18 months post injection, the mice were euthanized, and the eyes were collected and prepared for RNA-Seq. Compared to three uninfected control eyes, we identified 321 differentially expressed genes (DEGs) in six infected eyes. Using the QIAGEN Ingenuity Pathway Analysis (QIAGEN IPA), we identified 17 affected canonical pathways, 10 of which function in neuroretinal signaling, with the majority of DEGs being downregulated, while 7 pathways function in upregulated immune/inflammatory responses. Retinal and epithelial cell death pathways involving both apoptosis and necroptosis were also activated. MCMV ocular latency is associated with upregulation of immune and inflammatory responses and downregulation of multiple neuroretinal signaling pathways. Cell death signaling pathways are also activated and contribute to the degeneration of photoreceptors, RPE, and choroidal capillaries. FAU - Zhang, Xinyan AU - Zhang X AD - Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA. AD - James and Jean Vision Discovery Institute, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA. FAU - Xu, Jinxian AU - Xu J AD - Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA. AD - James and Jean Vision Discovery Institute, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA. FAU - Marshall, Brendan AU - Marshall B AD - Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA. FAU - Dong, Zheng AU - Dong Z AUID- ORCID: 0000-0003-3538-8095 AD - Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA. AD - Charlie Norwood VA Medical Center, Augusta, GA 30904, USA. FAU - Liu, Yutao AU - Liu Y AUID- ORCID: 0000-0003-2870-4504 AD - Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA. AD - James and Jean Vision Discovery Institute, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA. AD - Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA. FAU - Espinosa-Heidmann, Diego G AU - Espinosa-Heidmann DG AD - James and Jean Vision Discovery Institute, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA. AD - Department of Ophthamology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA. FAU - Zhang, Ming AU - Zhang M AUID- ORCID: 0000-0002-4012-3932 AD - Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA. AD - James and Jean Vision Discovery Institute, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA. LA - eng GR - P30 EY031631/EY/NEI NIH HHS/United States GR - R01 EY023242/EY/NEI NIH HHS/United States GR - R21 EY028671/EY/NEI NIH HHS/United States GR - RO1 EY026642/EY/NEI NIH HHS/United States PT - Journal Article DEP - 20230221 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 SB - IM MH - Mice MH - Animals MH - Mice, Inbred BALB C MH - *Eye Infections, Viral/metabolism/pathology MH - *Cytomegalovirus Infections MH - Choroid/metabolism MH - *Muromegalovirus/physiology MH - Gene Expression Profiling PMC - PMC10001583 OTO - NOTNLM OT - RNA sequencing OT - age-related macular degeneration OT - cytomegalovirus OT - degeneration OT - inflammation OT - latency COIS- The authors declare no conflict of interest. EDAT- 2023/03/12 06:00 MHDA- 2023/03/15 06:00 PMCR- 2023/02/21 CRDT- 2023/03/11 01:15 PHST- 2023/01/25 00:00 [received] PHST- 2023/02/16 00:00 [revised] PHST- 2023/02/17 00:00 [accepted] PHST- 2023/03/11 01:15 [entrez] PHST- 2023/03/12 06:00 [pubmed] PHST- 2023/03/15 06:00 [medline] PHST- 2023/02/21 00:00 [pmc-release] AID - ijms24054322 [pii] AID - ijms-24-04322 [pii] AID - 10.3390/ijms24054322 [doi] PST - epublish SO - Int J Mol Sci. 2023 Feb 21;24(5):4322. doi: 10.3390/ijms24054322.