Cellular senescence is associated with human retinal microaneurysm formation during aging
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- dc.contributor.author López-Luppo, Marianaca
- dc.contributor.author Catita, Joanaca
- dc.contributor.author Ramos, Davidca
- dc.contributor.author Navarro, Marcca
- dc.contributor.author Carretero, Anaca
- dc.contributor.author Mendes Jorge, Luísaca
- dc.contributor.author Muñoz Cánoves, Pura, 1962-ca
- dc.contributor.author Rodriguez-Baeza, Alfonsoca
- dc.contributor.author Nacher, Víctorca
- dc.contributor.author Ruberte, Jesúsca
- dc.date.accessioned 2017-11-06T17:40:21Z
- dc.date.available 2017-11-06T17:40:21Z
- dc.date.issued 2017
- dc.description.abstract Purpose: Microaneurysms are present in healthy old-age human retinas. However, to date, no age-related pathogenic mechanism has been implicated in their formation. Here, cellular senescence, a hallmark of aging and several age-related diseases, has been analyzed in the old-age human retina and in the retina of a progeric mouse. Methods: Retinas were obtained from 17 nondiabetic donors and from mice deficient in Bmi1. Cellular senescence was analyzed by immunohistochemistry, senescent-associated β-galactosidase activity assay, Sudan black B staining, conventional transmission electron microscopy, and immunoelectronmicroscopy. Results: Neurons, but not neuroglia, and blood vessels undergo cellular senescence in the old-age human retina. The canonical senescence markers p16, p53, and p21 were up-regulated and coexisted with apoptosis in old-age human microaneurysms. Senescent endothelial cells were discontinuously covered by fibronectin, and p16 colocalized with the β1 subunit of fibronectin receptor α5β1 integrin under the endothelial cellular membrane, suggesting anoikis as a mechanism involved in endothelial cell apoptosis. In a progeric mouse model deficient in Bmi1, where p21 was overexpressed, the retinal blood vessels displayed an aging phenotype characterized by enlarged caveolae and lipofuscin accumulation. Although mouse retina is not prone to develop microaneurysms, Bmi1-deficient mice presented abundant retinal microaneurysms. Conclusions: Together, these results uncover cellular senescence as a player during the formation of microaneurysms in old-age human retinas.
- dc.format.mimetype application/pdfca
- dc.identifier.citation López-Luppo M, Catita J, Ramos D, Navarro M, Carretero A, Mendes-Jorge L et al. Cellular senescence is associated with human retinal microaneurysm formation during aging. Invest Ophthalmol Vis Sci. 2017 Jun 1;58(7):2832-42. DOI: 10.1167/iovs.16-20312
- dc.identifier.doi http://dx.doi.org/10.1167/iovs.16-20312
- dc.identifier.issn 0146-0404
- dc.identifier.uri http://hdl.handle.net/10230/33151
- dc.language.iso eng
- dc.publisher Association for Research in Vision and Ophthalmology (ARVO)ca
- dc.relation.ispartof Investigative Ophthalmology & Visual Science. 2017 Jun 1;58(7):2832-42
- dc.rights © Copyright 2017 The Authors. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
- dc.subject.keyword Retina
- dc.subject.keyword Microaneurysms
- dc.subject.keyword Cellular senescence
- dc.title Cellular senescence is associated with human retinal microaneurysm formation during agingca
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion