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Activation of caspase-1-mediated canonical pyroptosis takes place via formation of multi-protein cytoplasmic immune signaling complexes known as inflammasomes. Because we have shown previously that the canonical pyroptosis pathway plays a significant role in the pathogenesis of experimental murine cytomegalovirus (MCMV) retinal necrosis in mice with retrovirus-induced immunosuppression (MAIDS), we performed additional studies to determine whether this pathogenic involvement extends to inflammasomes as initiators of the canonical pyroptosis pathway. Initial studies demonstrated significant transcription of three different pyroptosis-associated inflammasomes, NLRP3, NLRP1b, and AIM2, within the ocular compartments of MCMV-infected eyes of MAIDS mice. Subsequent histopathologic findings revealed MCMV-infected eyes of groups of NLRP3\u2212\/\u2212 MAIDS mice, NLRP1b\u2212\/\u2212 MAIDS mice, or AIM2\u2212\/\u2212 MAIDS mice each exhibited a similar atypical retinal pathology characterized by loss of photoreceptors and proliferation and\/or loss of retinal pigmented epithelium but with relative sparing of the neurosensory retina, an outcome different from typical full-thickness retinal necrosis of MCMV-infected eyes of wildtype MAIDS mice. We conclude that multiple inflammasomes are individually stimulated within MCMV-infected eyes of MAIDS mice and each independently contributes to MAIDS-related MCMV full-thickness retinal necrosis pathogenesis.<\/jats:p>","DOI":"10.3390\/pathogens14090879","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T08:04:15Z","timestamp":1756886655000},"page":"879","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["New Insights into the Pathogenesis of Experimental Cytomegalovirus Retinal Necrosis with an Emphasis on Inflammasomes and Pyroptosis"],"prefix":"10.3390","volume":"14","author":[{"given":"Richard D.","family":"Dix","sequence":"first","affiliation":[{"name":"Viral Immunology Center, Department of Biology, Georgia State University, Atlanta, GA 30303, USA"},{"name":"Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4715-734X","authenticated-orcid":false,"given":"Jessica J.","family":"Carter","sequence":"additional","affiliation":[{"name":"Viral Immunology Center, Department of Biology, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3061-9942","authenticated-orcid":false,"given":"Heather","family":"Koehler","sequence":"additional","affiliation":[{"name":"School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Louisiana State University, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1089\/jop.2016.0140","article-title":"Cytomegalovirus retinitis: A review","volume":"33","author":"Port","year":"2017","journal-title":"J. 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