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Loss of TRPV2-mediated blood flow autoregulation recapitulates diabetic retinopathy in rats
Loss of retinal blood flow autoregulation is an early feature of diabetes that precedes the development of clinically recognizable diabetic retinopathy (DR). Retinal blood flow autoregulation is mediated by the myogenic response of the retinal arterial vessels, a process that is initiated by the str...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9675469/ https://www.ncbi.nlm.nih.gov/pubmed/36134661 http://dx.doi.org/10.1172/jci.insight.155128 |
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author | O’Hare, Michael Esquiva, Gema McGahon, Mary K. Hombrebueno, Jose Manuel Romero Augustine, Josy Canning, Paul Edgar, Kevin S. Barabas, Peter Friedel, Thomas Cincolà, Patrizia Henry, Jennifer Mayne, Katie Ferrin, Hannah Stitt, Alan W. Lyons, Timothy J. Brazil, Derek P. Grieve, David J. McGeown, J. Graham Curtis, Tim M. |
author_facet | O’Hare, Michael Esquiva, Gema McGahon, Mary K. Hombrebueno, Jose Manuel Romero Augustine, Josy Canning, Paul Edgar, Kevin S. Barabas, Peter Friedel, Thomas Cincolà, Patrizia Henry, Jennifer Mayne, Katie Ferrin, Hannah Stitt, Alan W. Lyons, Timothy J. Brazil, Derek P. Grieve, David J. McGeown, J. Graham Curtis, Tim M. |
author_sort | O’Hare, Michael |
collection | PubMed |
description | Loss of retinal blood flow autoregulation is an early feature of diabetes that precedes the development of clinically recognizable diabetic retinopathy (DR). Retinal blood flow autoregulation is mediated by the myogenic response of the retinal arterial vessels, a process that is initiated by the stretch‑dependent activation of TRPV2 channels on the retinal vascular smooth muscle cells (VSMCs). Here, we show that the impaired myogenic reaction of retinal arterioles from diabetic animals is associated with a complete loss of stretch‑dependent TRPV2 current activity on the retinal VSMCs. This effect could be attributed, in part, to TRPV2 channel downregulation, a phenomenon that was also evident in human retinal VSMCs from diabetic donors. We also demonstrate that TRPV2 heterozygous rats, a nondiabetic model of impaired myogenic reactivity and blood flow autoregulation in the retina, develop a range of microvascular, glial, and neuronal lesions resembling those observed in DR, including neovascular complexes. No overt kidney pathology was observed in these animals. Our data suggest that TRPV2 dysfunction underlies the loss of retinal blood flow autoregulation in diabetes and provide strong support for the hypothesis that autoregulatory deficits are involved in the pathogenesis of DR. |
format | Online Article Text |
id | pubmed-9675469 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-96754692022-11-21 Loss of TRPV2-mediated blood flow autoregulation recapitulates diabetic retinopathy in rats O’Hare, Michael Esquiva, Gema McGahon, Mary K. Hombrebueno, Jose Manuel Romero Augustine, Josy Canning, Paul Edgar, Kevin S. Barabas, Peter Friedel, Thomas Cincolà, Patrizia Henry, Jennifer Mayne, Katie Ferrin, Hannah Stitt, Alan W. Lyons, Timothy J. Brazil, Derek P. Grieve, David J. McGeown, J. Graham Curtis, Tim M. JCI Insight Research Article Loss of retinal blood flow autoregulation is an early feature of diabetes that precedes the development of clinically recognizable diabetic retinopathy (DR). Retinal blood flow autoregulation is mediated by the myogenic response of the retinal arterial vessels, a process that is initiated by the stretch‑dependent activation of TRPV2 channels on the retinal vascular smooth muscle cells (VSMCs). Here, we show that the impaired myogenic reaction of retinal arterioles from diabetic animals is associated with a complete loss of stretch‑dependent TRPV2 current activity on the retinal VSMCs. This effect could be attributed, in part, to TRPV2 channel downregulation, a phenomenon that was also evident in human retinal VSMCs from diabetic donors. We also demonstrate that TRPV2 heterozygous rats, a nondiabetic model of impaired myogenic reactivity and blood flow autoregulation in the retina, develop a range of microvascular, glial, and neuronal lesions resembling those observed in DR, including neovascular complexes. No overt kidney pathology was observed in these animals. Our data suggest that TRPV2 dysfunction underlies the loss of retinal blood flow autoregulation in diabetes and provide strong support for the hypothesis that autoregulatory deficits are involved in the pathogenesis of DR. American Society for Clinical Investigation 2022-09-22 /pmc/articles/PMC9675469/ /pubmed/36134661 http://dx.doi.org/10.1172/jci.insight.155128 Text en © 2022 O’Hare et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article O’Hare, Michael Esquiva, Gema McGahon, Mary K. Hombrebueno, Jose Manuel Romero Augustine, Josy Canning, Paul Edgar, Kevin S. Barabas, Peter Friedel, Thomas Cincolà, Patrizia Henry, Jennifer Mayne, Katie Ferrin, Hannah Stitt, Alan W. Lyons, Timothy J. Brazil, Derek P. Grieve, David J. McGeown, J. Graham Curtis, Tim M. Loss of TRPV2-mediated blood flow autoregulation recapitulates diabetic retinopathy in rats |
title | Loss of TRPV2-mediated blood flow autoregulation recapitulates diabetic retinopathy in rats |
title_full | Loss of TRPV2-mediated blood flow autoregulation recapitulates diabetic retinopathy in rats |
title_fullStr | Loss of TRPV2-mediated blood flow autoregulation recapitulates diabetic retinopathy in rats |
title_full_unstemmed | Loss of TRPV2-mediated blood flow autoregulation recapitulates diabetic retinopathy in rats |
title_short | Loss of TRPV2-mediated blood flow autoregulation recapitulates diabetic retinopathy in rats |
title_sort | loss of trpv2-mediated blood flow autoregulation recapitulates diabetic retinopathy in rats |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9675469/ https://www.ncbi.nlm.nih.gov/pubmed/36134661 http://dx.doi.org/10.1172/jci.insight.155128 |
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