Corneal endothelial cells provide evidence of accelerated cellular senescence associated with HIV infection: a case-control study

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dc.contributor.authorPathai, Sophiaen_ZA
dc.contributor.authorLawn, Stephen Den_ZA
dc.contributor.authorShiels, Paul Gen_ZA
dc.contributor.authorWeiss, Helen Aen_ZA
dc.contributor.authorCook, Colinen_ZA
dc.contributor.authorWood, Robinen_ZA
dc.contributor.authorGilbert, Clare Een_ZA
dc.date.accessioned2015-11-23T12:25:41Z
dc.date.available2015-11-23T12:25:41Z
dc.date.issued2013en_ZA
dc.description.abstractBACKGROUND: Cellular senescence may be a key factor in HIV-related premature biological aging. We assessed features of the corneal endothelium that are known to be associated with biological aging, and cellular senescence markers in HIV-infected adults. METHODS: Case-control study of 242 HIV-infected adults and 249 matched controls. Using specular microscopy, the corneal endothelium was assessed for features of aging (low endothelial cell density [ECD], high variation in cell size, and low hexagonality index). Data were analysed by multivariable regression. CDKN2A expression (a cell senescence mediator) was measured in peripheral blood leukocytes and 8-hydroxy-2′-deoxyguanosine (8-OHDG; an oxidative DNA damage marker) levels were measured in plasma. RESULTS: The median age of both groups was 40 years. Among HIV-infected adults, 88% were receiving antiretroviral therapy (ART); their median CD4 count was 468 cells/µL. HIV infection was associated with increased odds of variation in cell size (OR = 1.67; 95% CI: 1.00-2.78, p = 0.04). Among HIV-infected participants, low ECD was independently associated with current CD4 count <200 cells/µL (OR = 2.77; 95%CI: 1.12-6.81, p = 0.03). In participants on ART with undetectable viral load, CDKN2A expression and 8-OHDG levels were higher in those with accelerated aging, as reflected by lower ECD. CONCLUSIONS: The corneal endothelium shows features consistent with HIV-related accelerated senescence, especially among those with poor immune recovery.en_ZA
dc.identifier.apacitationPathai, S., Lawn, S. D., Shiels, P. G., Weiss, H. A., Cook, C., Wood, R., & Gilbert, C. E. (2013). Corneal endothelial cells provide evidence of accelerated cellular senescence associated with HIV infection: a case-control study. <i>PLoS One</i>, http://hdl.handle.net/11427/15277en_ZA
dc.identifier.chicagocitationPathai, Sophia, Stephen D Lawn, Paul G Shiels, Helen A Weiss, Colin Cook, Robin Wood, and Clare E Gilbert "Corneal endothelial cells provide evidence of accelerated cellular senescence associated with HIV infection: a case-control study." <i>PLoS One</i> (2013) http://hdl.handle.net/11427/15277en_ZA
dc.identifier.citationPathai, S., Lawn, S. D., Shiels, P. G., Weiss, H. A., Cook, C., Wood, R., & Gilbert, C. E. (2013). Corneal endothelial cells provide evidence of accelerated cellular senescence associated with HIV infection: a case-control study. PloS one, 8(2), e57422. doi:10.1371/journal.pone.0057422en_ZA
dc.identifier.ris TY - Journal Article AU - Pathai, Sophia AU - Lawn, Stephen D AU - Shiels, Paul G AU - Weiss, Helen A AU - Cook, Colin AU - Wood, Robin AU - Gilbert, Clare E AB - BACKGROUND: Cellular senescence may be a key factor in HIV-related premature biological aging. We assessed features of the corneal endothelium that are known to be associated with biological aging, and cellular senescence markers in HIV-infected adults. METHODS: Case-control study of 242 HIV-infected adults and 249 matched controls. Using specular microscopy, the corneal endothelium was assessed for features of aging (low endothelial cell density [ECD], high variation in cell size, and low hexagonality index). Data were analysed by multivariable regression. CDKN2A expression (a cell senescence mediator) was measured in peripheral blood leukocytes and 8-hydroxy-2′-deoxyguanosine (8-OHDG; an oxidative DNA damage marker) levels were measured in plasma. RESULTS: The median age of both groups was 40 years. Among HIV-infected adults, 88% were receiving antiretroviral therapy (ART); their median CD4 count was 468 cells/µL. HIV infection was associated with increased odds of variation in cell size (OR = 1.67; 95% CI: 1.00-2.78, p = 0.04). Among HIV-infected participants, low ECD was independently associated with current CD4 count <200 cells/µL (OR = 2.77; 95%CI: 1.12-6.81, p = 0.03). In participants on ART with undetectable viral load, CDKN2A expression and 8-OHDG levels were higher in those with accelerated aging, as reflected by lower ECD. CONCLUSIONS: The corneal endothelium shows features consistent with HIV-related accelerated senescence, especially among those with poor immune recovery. DA - 2013 DB - OpenUCT DO - 10.1371/journal.pone.0057422 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2013 T1 - Corneal endothelial cells provide evidence of accelerated cellular senescence associated with HIV infection: a case-control study TI - Corneal endothelial cells provide evidence of accelerated cellular senescence associated with HIV infection: a case-control study UR - http://hdl.handle.net/11427/15277 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15277
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0057422
dc.identifier.vancouvercitationPathai S, Lawn SD, Shiels PG, Weiss HA, Cook C, Wood R, et al. Corneal endothelial cells provide evidence of accelerated cellular senescence associated with HIV infection: a case-control study. PLoS One. 2013; http://hdl.handle.net/11427/15277.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDesmond Tutu HIV Centreen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2013 Pathai et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherEndothelial cellsen_ZA
dc.subject.otherCorneaen_ZA
dc.subject.otherSenescenceen_ZA
dc.subject.otherEyesen_ZA
dc.subject.otherHIV infectionsen_ZA
dc.subject.otherEndotheliumen_ZA
dc.subject.otherHIVen_ZA
dc.subject.otherWhite blood cellsen_ZA
dc.titleCorneal endothelial cells provide evidence of accelerated cellular senescence associated with HIV infection: a case-control studyen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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