Atypical cytomegalovirus retinal disease in pyroptosis-deficient mice with murine acquired immunodeficiency syndrome

Carter, Jessica J.; Nemeno, J.G.; Oh, Jay; Houghton, John E.; Dix, Richard D.

doi:10.1016/j.exer.2021.108651

Cited by 5 publications

(3 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While the innate response within these mice and their extreme susceptibility to viral infection of the retina is not completely understood, there appear to be changes in the cell death pathways and chemokines produced compared to those in wild-type mice and controls [ 141 ]. While retinal infections with cytomegalovirus appear and progress very differently from how ARN does clinically, cell death pathways are also broadly upregulated and a loss of caspase-1, a mediator of programmed cell death, results in atypical retinal disease [ 143 , 144 ]. In other neuronal tissues, cell death pathways also play an important role in limiting herpetic encephalitis [ 145 ].…”

Section: Infections Of the Posterior Segmentmentioning

confidence: 99%

The Host–Pathogen Interplay: A Tale of Two Stories within the Cornea and Posterior Segment

Dempsey

Conrady

2023

Microorganisms

View full text Add to dashboard Cite

Ocular infectious diseases are an important cause of potentially preventable vision loss and blindness. In the following manuscript, we will review ocular immunology and the pathogenesis of herpesviruses and Pseudomonas aeruginosa infections of the cornea and posterior segment. We will highlight areas of future research and what is currently known to promote bench-to-bedside discoveries to improve clinical outcomes of these debilitating ocular diseases.

show abstract

Section: Infections Of the Posterior Segmentmentioning

confidence: 99%

The Host–Pathogen Interplay: A Tale of Two Stories within the Cornea and Posterior Segment

Dempsey

Conrady

2023

Microorganisms

View full text Add to dashboard Cite

show abstract

“…Xu et al also provided evidence that the expression of pyroptosis-related inflammasomes, including NLRP3, NLRP4, NLRP6, and AIM2 were upregulated in the eyecups of the MCMV-infected mice [ 153 ]. Of greater significance, Carter et al recently demonstrated that although both pyroptosis and apoptosis occur in the ocular compartment of MCMV-infected mice with MAIDS, pyroptosis contributes far more than apoptosis toward the development of full-thickness retinal necrosis during the pathogenesis of MAIDS-related MCMV retinitis [ 14 ]. An atypical phenomenon was also observed in this research that the MCMV-infected eyes of MAIDS mice with caspase-1, GSDMD, or IL-18 deficiency did not develop full-thickness retinal necrosis but instead presented thickening and proliferation of the retinal pigmented epithelium layer with relative preservation of the neurosensory retina in contrast to wildtype MAIDS mice [ 14 ].…”

Section: Pyroptosis In Ocular Diseasesmentioning

confidence: 99%

Spotlight on pyroptosis: role in pathogenesis and therapeutic potential of ocular diseases

Chen

Rong

Xia

2022

J Neuroinflammation

View full text Add to dashboard Cite

Pyroptosis is a programmed cell death characterized by swift plasma membrane disruption and subsequent release of cellular contents and pro-inflammatory mediators (cytokines), including IL‐1β and IL‐18. It differs from other types of programmed cell death such as apoptosis, autophagy, necroptosis, ferroptosis, and NETosis in terms of its morphology and mechanism. As a recently discovered form of cell death, pyroptosis has been demonstrated to be involved in the progression of multiple diseases. Recent studies have also suggested that pyroptosis is linked to various ocular diseases. In this review, we systematically summarized and discussed recent scientific discoveries of the involvement of pyroptosis in common ocular diseases, including diabetic retinopathy, age-related macular degeneration, AIDS-related human cytomegalovirus retinitis, glaucoma, dry eye disease, keratitis, uveitis, and cataract. We also organized new and emerging evidence suggesting that pyroptosis signaling pathways may be potential therapeutic targets in ocular diseases, hoping to provide a summary of overall intervention strategies and relevant multi-dimensional evaluations for various ocular diseases, as well as offer valuable ideas for further research and development from the perspective of pyroptosis.

show abstract

“…In sharp contrast, none (0%) of MCMV-infected eyes of caspase-1 −/− MAIDS mice, GSDMD −/− MAIDS mice, or IL-18 −/− MAIDS mice developed full-thickness retinal necrosis. Instead, these animals exhibited an atypical pattern of retinal disease characterized by thickening and proliferation of the RPE layer with relative sparing of the neurosensory retina [ 83 ]. Surprisingly, MCMV-infected eyes of all groups of proptosis-deficient MAIDS mice harbored equivalent intraocular amounts of infectious virus as seen within MCMV-infected eyes of wildtype mice despite failure to develop full-thickness retinal necrosis.…”

Section: Insights Into Pathogenesismentioning

confidence: 99%

A Mouse Model That Mimics AIDS-Related Cytomegalovirus Retinitis: Insights into Pathogenesis

Carter

Dix

2021

Pathogens

Self Cite

View full text Add to dashboard Cite

With the appearance of the worldwide AIDS pandemic four decades ago came a number of debilitating opportunistic infections in patients immunosuppressed by the pathogenic human retrovirus HIV. Among these was a severe sight-threatening retinal disease caused by human cytomegalovirus (HCMV) that remains today a significant cause of vision loss and blindness in untreated AIDS patients without access or sufficient response to combination antiretroviral therapy. Early investigations of AIDS-related HCMV retinitis quickly characterized its hallmark clinical features and unique histopathologic presentation but did not begin to identify the precise virologic and immunologic events that allow the onset and development of this retinal disease during HIV-induced immunosuppression. Toward this end, several mouse models of experimental cytomegalovirus retinitis have been developed to provide new insights into the pathophysiology of HCMV retinitis during AIDS. Herein, we provide a summary and comparison of these mouse models of AIDS-related HCMV retinitis with particular emphasis on one mouse model developed in our laboratory in which mice with a murine acquired immunodeficiency syndrome (MAIDS) of murine retrovirus origin develops a reproducible and well characterized retinitis following intraocular infection with murine cytomegalovirus (MCMV). The MAIDS model of MCMV retinitis has advanced the discovery of many clinically relevant virologic and immunologic mechanisms of virus-induced retinal tissue destruction that are discussed and summarized in this review. These findings may extend to the pathogenesis of AIDS-related HCMV retinitis and other AIDS-related opportunistic virus infections.

show abstract

Atypical cytomegalovirus retinal disease in pyroptosis-deficient mice with murine acquired immunodeficiency syndrome

Cited by 5 publications

References 46 publications

The Host–Pathogen Interplay: A Tale of Two Stories within the Cornea and Posterior Segment

The Host–Pathogen Interplay: A Tale of Two Stories within the Cornea and Posterior Segment

Spotlight on pyroptosis: role in pathogenesis and therapeutic potential of ocular diseases

A Mouse Model That Mimics AIDS-Related Cytomegalovirus Retinitis: Insights into Pathogenesis

Contact Info

Product

Resources

About