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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2022
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.
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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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