Academic Journal

Loss of TRPV2-mediated blood flow autoregulation recapitulates diabetic retinopathy in rats

التفاصيل البيبلوغرافية
العنوان: Loss of TRPV2-mediated blood flow autoregulation recapitulates diabetic retinopathy in rats
المؤلفون: Michael O’Hare, Gema Esquiva, Mary K. McGahon, Jose Manuel Romero Hombrebueno, Josy Augustine, Paul Canning, Kevin S. Edgar, Peter Barabas, Thomas Friedel, Patrizia Cincolà, Jennifer Henry, Katie Mayne, Hannah Ferrin, Alan W. Stitt, Timothy J. Lyons, Derek P. Brazil, David J. Grieve, J. Graham McGeown, Tim M. Curtis
المصدر: JCI Insight, Vol 7, Iss 18 (2022)
بيانات النشر: American Society for Clinical investigation, 2022.
سنة النشر: 2022
المجموعة: LCC:Medicine
مصطلحات موضوعية: Ophthalmology, Vascular biology, Medicine
الوصف: 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2379-3708
Relation: https://doaj.org/toc/2379-3708
DOI: 10.1172/jci.insight.155128
URL الوصول: https://doaj.org/article/a8eb7a938da94f0fbc793be40b8dc476
رقم الانضمام: edsdoj.8eb7a938da94f0fbc793be40b8dc476
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:23793708
DOI:10.1172/jci.insight.155128