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Journal of Neuroinflammation Jul 2022Pyroptosis is a programmed cell death characterized by swift plasma membrane disruption and subsequent release of cellular contents and pro-inflammatory mediators... (Review)
Review
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.
Topics: Apoptosis; Humans; Inflammasomes; Inflammation Mediators; Necroptosis; Pyroptosis
PubMed: 35836195
DOI: 10.1186/s12974-022-02547-2 -
Viruses Jan 2023Little is known regarding anterior uveitis (AU), the most common ocular disease associated with cytomegalovirus (CMV) infection in immunocompetent populations. CMV AU is... (Review)
Review
Little is known regarding anterior uveitis (AU), the most common ocular disease associated with cytomegalovirus (CMV) infection in immunocompetent populations. CMV AU is highly prevalent in Asia, with a higher incidence in men. Clinically, it manifests mainly as anterior chamber inflammation and elevated intraocular pressure (IOP). Acute CMV AU may resemble Posner-Schlossman syndrome with its recurrent hypertensive iritis, while chronic CMV AU may resemble Fuchs uveitis because of its elevated IOP. Without prompt treatment, it may progress to glaucoma; therefore, early diagnosis is critical to prognosis. Knowledge regarding clinical features and aqueous humor analyses can facilitate accurate diagnoses; so, we compared and summarized these aspects. Early antiviral treatment reduces the risk of a glaucoma surgery requirement, and therapeutic effects vary based on drug delivery. Both oral valganciclovir and topical ganciclovir can produce positive clinical outcomes, and higher concentration and frequency are beneficial in chronic CMV retinitis. An extended antiviral course could prevent relapses, but should be limited to 6 months to prevent drug resistance and side effects. In this review, we have systematically summarized the pathogenesis, clinical features, diagnostic and therapeutic aspects, and immunological mechanisms of CMV AU with the goal of providing a theoretical foundation for early clinical diagnosis and treatment.
Topics: Male; Humans; Cytomegalovirus; Eye Infections, Viral; Ganciclovir; Antiviral Agents; Cytomegalovirus Infections; Uveitis, Anterior; Glaucoma; Retrospective Studies; DNA, Viral
PubMed: 36680225
DOI: 10.3390/v15010185 -
Microorganisms Dec 2019Cytomegalovirus retinitis (CMVR) is a severe, vision-threatening disease that primarily affects immunosuppressed patients. CMVR is the most common ocular opportunistic... (Review)
Review
Cytomegalovirus retinitis (CMVR) is a severe, vision-threatening disease that primarily affects immunosuppressed patients. CMVR is the most common ocular opportunistic infection in human immunodeficiency virus (HIV) infected patients and is the leading cause of blindness in this group; however, the incidence of CMVR in HIV patients has dramatically decreased with antiretroviral therapy. Other causes of immunosuppression, including organ transplantation, hematologic malignancies, and iatrogenic immunosuppression, can also lead to the development of CMVR. Herein, we describe the pathogenesis of CMVR and compare clinical features, epidemiology, and risk factors in HIV and non-HIV infected individuals with CMVR.
PubMed: 31905656
DOI: 10.3390/microorganisms8010055 -
Viruses Apr 2022Human cytomegalovirus (HCMV) is a herpesvirus that alternates lytic and latent infection, infecting between 40 and 95% of the population worldwide, usually without... (Review)
Review
Human cytomegalovirus (HCMV) is a herpesvirus that alternates lytic and latent infection, infecting between 40 and 95% of the population worldwide, usually without symptoms. During its lytic cycle, HCMV can result in fever, asthenia, and, in some cases, can lead to severe symptoms such as hepatitis, pneumonitis, meningitis, retinitis, and severe cytomegalovirus disease, especially in immunocompromised individuals. Usually, the host immune response keeps the virus in a latent stage, although HCMV can reactivate in an inflammatory context, which could result in sequential lytic/latent viral cycles during the lifetime and thereby participate in the HCMV genomic diversity in humans and the high level of HCMV intrahost genomic variability. The oncomodulatory role of HCMV has been reported, where the virus will favor the development and spread of cancerous cells. Recently, an oncogenic role of HCMV has been highlighted in which the virus will directly transform primary cells and might therefore be defined as the eighth human oncovirus. In light of these new findings, it is critical to understand the role of the immune landscape, including the tumor microenvironment present in HCMV-harboring tumors. Finally, the oncomodulatory/oncogenic potential of HCMV could lead to the development of novel adapted therapeutic approaches against HCMV, especially since immunotherapy has revolutionized cancer therapeutic strategies and new therapeutic approaches are actively needed, particularly to fight tumors of poor prognosis.
Topics: Carcinogenesis; Cytomegalovirus; Cytomegalovirus Infections; Humans; Immunotherapy; Neoplasms; Oncogenes; Tumor Microenvironment
PubMed: 35458542
DOI: 10.3390/v14040812 -
American Journal of Ophthalmology Aug 2021The purpose of this study was to determine classification criteria for cytomegalovirus (CMV) retinitis.
PURPOSE
The purpose of this study was to determine classification criteria for cytomegalovirus (CMV) retinitis.
DESIGN
Machine learning of cases with CMV retinitis and 4 other infectious posterior/ panuveitides.
METHODS
Cases of infectious posterior/panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on diagnosis using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used in the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the infectious posterior/panuveitides. The resulting criteria were evaluated in the validation set.
RESULTS
A total of 803 cases of infectious posterior/panuveitides, including 211 cases of CMV retinitis, were evaluated by machine learning. Key criteria for CMV retinitis included: 1) necrotizing retinitis with indistinct borders due to numerous small satellites; 2) evidence of immune compromise; and either 3) a characteristic clinical appearance, or 4) positive polymerase chain reaction assay results for CMV from an intraocular specimen. Characteristic appearances for CMV retinitis included: 1) wedge-shaped area of retinitis; 2) hemorrhagic retinitis; or 3) granular retinitis. Overall accuracy for infectious posterior/panuveitides was 92.1% in the training set and 93.3% (95% confidence interval: 88.2-96.3) in the validation set. The misclassification rates for CMV retinitis were 6.9% in the training set and 6.3% in the validation set.
CONCLUSIONS
The criteria for CMV retinitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.
Topics: Adult; Cytomegalovirus; Cytomegalovirus Retinitis; DNA, Viral; Eye Infections, Viral; Female; Humans; Machine Learning; Male; Middle Aged
PubMed: 33845015
DOI: 10.1016/j.ajo.2021.03.051 -
Journal of Ophthalmic Inflammation and... Oct 2021Cytomegalovirus (CMV) retinitis in patients with Non-Hodgkin's Lymphoma (NHL) can occur even in the presence of high CD 4 counts and can behave differently when compared...
BACKGROUND
Cytomegalovirus (CMV) retinitis in patients with Non-Hodgkin's Lymphoma (NHL) can occur even in the presence of high CD 4 counts and can behave differently when compared to CMV retinitis in human immunodeficiency (HIV) patients. It, therefore, becomes important to understand its varied presentations and the challenges in management of these cases. The aim of this study was to analyse the various patterns of presentations and outcomes of CMV Retinitis in patients with NHL.
STUDY DESIGN
A retrospective chart review of seven eyes of four patients of NHL presenting with CMV retinitis between June 2017 and May 2020 was done.
METHODS
Clinical patterns of CMV Retinitis, CD4 counts at the time of presentation and the duration of treatment along with recurrences and time for recurrence of retinitis were assessed.
RESULTS
Granular or indolent retinitis (6 out of 7 eyes) was the commonest form of CMV retinitis in patients of NHL. Three patients had a presenting CD4 count above 150 cells/mm and none of them were below 50 cells/mm. Floaters were the commonest presenting complaint. All patients had vitritis and majority of the patients (3 out of 4) had anterior chamber (AC) inflammation. Two out of the 4 patients had a recurrence (mean time 33.8 days) after stopping the maintenance phase of ganciclovir and one patient had significant myelosuppression related to oral valganciclovir which required discontinuation of the drug.
CONCLUSION
CMV retinitis in NHL patients is usually of an indolent or granular type and can occur even in the presence of high CD4 counts as compared to patients with HIV. These patients may require a long term maintenance in view of frequent recurrences after discontinuation of treatment.
PubMed: 34611773
DOI: 10.1186/s12348-021-00257-z -
Southern African Journal of HIV Medicine 2022South Africa's public antiretroviral treatment (ART) programme has undergone progressive changes since its introduction in 2004. The effect of this on the burden of the...
BACKGROUND
South Africa's public antiretroviral treatment (ART) programme has undergone progressive changes since its introduction in 2004. The effect of this on the burden of the AIDS-defining opportunistic infection, cytomegalovirus retinitis (CMVR), in SA, has not been fully appreciated.
OBJECTIVES
To determine the effect of ART availability in the public sector of SA on the trend in the number of cases of newly diagnosed CMVR over time.
METHODS
This is a retrospective study from 01 November 2002 to 31 August 2017 that took place at a tertiary hospital in the KwaZulu-Natal (KZN) province.
RESULTS
A total of 383 participants were included in the study, with 60.1% being female and 94% of black African origin. The mean age of patients was 34.08 years (SD ± 7.24). A linear trend model suggested an overall linear decrease in the number of new cases of CMVR per year ( of 0.67). The average number of new cases of CMVR per year prior to ART being available to all persons living with HIV (PLWH) with a CD4+ ≤ 350 cells/μL and after was 34 and 13, respectively, and the difference (61.76%) between these values was statistically significant, = 0.001. The median CD4+ count at diagnosis of CMVR was 22 (interquartile range: 9-51.25) cells/μL. An overall 51% of patients in this study were on ART at diagnosis of CMVR. There was a higher proportion of patients on ART ≤ 6 months (63.3%), compared with those on ART > 6 months (36.7%), and the difference was statistically significant, < 0.01.
CONCLUSION
ART has resulted in a decrease in the burden of CMVR on ophthalmic services for many in KZN, particularly following the introduction of ART for all PLWH with a CD4 ≤ 350 cells/μL.
PubMed: 35399749
DOI: 10.4102/sajhivmed.v23i1.1322 -
Frontiers in Genetics 2019Human cytomegalovirus (HCMV) is a ubiquitous herpes virus (human herpes virus 5) with the highest morbidity and mortality rates compared to other herpes viruses. Risk... (Review)
Review
Human cytomegalovirus (HCMV) is a ubiquitous herpes virus (human herpes virus 5) with the highest morbidity and mortality rates compared to other herpes viruses. Risk groups include very young, elderly, transplant recipient, and immunocompromised individuals. HCMV may cause retinitis, encephalitis, hepatitis, esophagitis, colitis, pneumonia, neonatal infection sequelae, inflammatory, and age-related diseases. With an arsenal of genes in its large genome dedicated to host immune evasion, HCMV can block intrinsic cellular defenses and interfere with cellular immune responses. HCMV also encodes chemokines, chemokine receptors, and cytokines. Therefore, genes involved in human viral defense mechanisms and those encoding proteins targeted by the CMV proteins are candidates for host control of CMV infection and reactivation. Although still few in number, host genetic studies are producing valuable insights into biological processes involved in HCMV pathogenesis and HCMV-related diseases. For example, genetic variants in the immunoglobulin GM light chain can influence the antibody responsiveness to CMV glycoprotein B and modify risk of HCMV-related diseases. Moreover, CMV infection following organ transplantation has been associated with variants in genes encoding toll-like receptors (TLRs), programmed death-1 (), and interleukin-12p40 (). A KIR haplotype (2DS4+) is proposed to be protective for CMV activation among hematopoietic stem cell transplant patients. Polymorphisms in the interferon lambda 3/4 () region are shown to influence susceptibility to CMV replication among solid organ transplant patients. Interestingly, the region is also associated with AIDS-related CMV retinitis susceptibility in HIV-infected patients. Likewise, interleukin-10 receptor 1 () variants are shown to influence CMV retinitis development in patients with AIDS. Results from genome-wide association studies suggest a possible role for microtubule network and retinol metabolism in anti-CMV antibody response. Nevertheless, further genetic epidemiological studies with large cohorts, functional studies on the numerous HCMV genes, and immune response to chronic and latent states of infection that contribute to HCMV persistence are clearly necessary to elucidate the genetic mechanisms of CMV infection, reactivation, and pathogenesis.
PubMed: 31396258
DOI: 10.3389/fgene.2019.00616 -
Annals of Eye Science Mar 2022Cytomegalovirus (CMV) retinitis is an opportunistic infection that has traditionally affected those who have HIV/AIDS or immunosuppressed individuals. CMV retinitis...
Cytomegalovirus (CMV) retinitis is an opportunistic infection that has traditionally affected those who have HIV/AIDS or immunosuppressed individuals. CMV retinitis previously infected one-third of AIDS patients in the pre-highly active antiretroviral therapy (HAART) era, but since HAART, Western countries have seen an 80% decrease in the incidence of the disease. More recently, CMV retinitis has been reported in patients who are immunosuppressed, often due to chemotherapy or immunomodulatory medications. The diagnosis of CMV retinitis is often suspected based on clinical findings, with polymerase chain reaction for confirmation of CMV, especially in atypical cases. Highly active antiretroviral therapy and anti-CMV medications (systemic or local) remain the mainstay of treatment. However, for those who are not responsive to HAART, CMV retinitis remains a challenge, and can still lead to significant vision loss. Moreover, a regimen of anti-CMV medications can sometimes lead to viral resistance or organ toxicity. Complications such as immune recovery retinitis and rhegmatogenous retinal detachments continue to threaten the vision of patients who develop CMV retinitis. These complications can arise following initiation of treatment or if patients show disease progression. Proper vision screening for CMV retinitis in immunosuppressed patients at-risk is necessary for early detection and treatment.
PubMed: 35498636
DOI: 10.21037/aes-21-18