Loss of TRPV2-mediated blood flow autoregulation recapitulates diabetic retinopathy in rats.
Loss of TRPV2-mediated blood flow autoregulation recapitulates diabetic retinopathy in rats.
复制标题
DOI：
10.1172/jci.insight.155128
复制
发表时间：
2022-09-22
期刊：
影响因子：
8
通讯作者：
Curtis, Tim M.
中科院分区：
文献类型：
--
作者：
O'Hare, Michael;Esquiva, Gema;McGahon, Mary K.;Hombrebueno, Jose Manuel Romero;Augustine, Josy;Canning, Paul;Edgar, Kevin S.;Barabas, Peter;Friedel, Thomas;Cincola, 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.
视网膜血流自动调节的丧失是糖尿病的早期特征，其先于临床可识别的糖尿病视网膜病变（DR）的发展。视网膜血流自动调节由视网膜动脉血管的肌源性反应介导，这一过程由视网膜血管平滑肌细胞（VSMC）上TRPV 2通道的牵张依赖性激活启动。在这里，我们发现糖尿病动物视网膜小动脉的肌源性反应受损与视网膜VSMC上牵张依赖性TRPV 2电流活性的完全丧失有关。这种效应可能部分归因于TRPV2通道下调，这一现象在来自糖尿病供体的人视网膜VSMC中也很明显。我们还证明，TRPV2杂合子大鼠，一个非糖尿病模型受损的肌源性反应和血流自动调节在视网膜，开发一系列的微血管，神经胶质细胞和神经元病变类似的DR中观察到的，包括新生血管复合体。在这些动物中未观察到明显的肾脏病理学。我们的数据表明，TRPV2功能障碍是糖尿病视网膜血流自动调节功能丧失的基础，并为DR发病机制中涉及自动调节缺陷的假设提供了强有力的支持。
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.
登录
查看更多内容
影响因子：
4.6
作者：
Katanosaka K;Takatsu S;Mizumura K;Naruse K;Katanosaka Y
通讯作者：
Katanosaka Y
影响因子：
3.4
作者：
Ahn, Changhwan;Choi, Jong-Sam;Jeung, Eui-Bae
通讯作者：
Jeung, Eui-Bae
影响因子：
4.4
作者：
Fukushi, J;Ono, M;Kuwano, W
通讯作者：
Kuwano, W
影响因子：
6
作者：
Gardiner, TA;Gibson, DS;Stitt, AW
通讯作者：
Stitt, AW
影响因子：
4.8
作者：
Kevil, CG;Orr, AW;Bullard, DC
通讯作者：
Bullard, DC