VEGF Mediates Retinal Müller Cell Viability and Neuroprotection through BDNF in Diabetes.
VEGF Mediates Retinal Müller Cell Viability and Neuroprotection through BDNF in Diabetes.
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VEGF通过BDNF介导糖尿病视网膜上皮细胞活力和神经保护。
DOI：
10.3390/biom11050712
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发表时间：
2021-05-10
期刊：
影响因子：
5.5
通讯作者：
Zhu M
中科院分区：
文献类型：
--
作者：
Le YZ;Xu B;Chucair-Elliott AJ;Zhang H;Zhu M
为探讨血管内皮生长因子(VEGF)和脑源性神经营养因子(BDNF)在糖尿病视网膜病变(DR)中对Müller细胞(MC)活性和神经保护作用的机制，我们检测了血管内皮生长因子(VEGF)在MC活性和BDNF产生中的作用，以及BDNF对糖尿病条件下MC活性的影响。用小鼠原代MC和大鼠MC系rMC1的细胞研究糖尿病条件下MC的活性和BDNF的产生。在小鼠中证实了血管内皮生长因子刺激的脑源性神经营养因子的产生。用siRNA基因敲除技术研究BDNF介导的MC存活的机制。在糖尿病条件下，重组血管内皮生长因子(RVEGF)以剂量依赖的方式刺激MC活力和BDNF的产生。RBDNF还以剂量依赖的方式支持MC活性。靶向BDNF受体原肌球蛋白受体激酶B(TRK-B)的siRNA敲除显著下调丝氨酸/苏氨酸特异性蛋白激酶(AKT)和细胞外信号调节激酶(ERK)的激活(磷酸化)形式，这两个经典的生存和增殖介质。最后，rBDNF挽救了糖尿病条件下TrkB siRNA转基因细胞MC活性的丧失。我们的结果首次提供了直接证据，证明血管内皮生长因子是糖尿病患者脑源性神经营养因子产生的积极调节因子。这些信息对于在DR和缺氧性视网膜疾病中发展BDNF介导的神经保护，以及改善这些血-视网膜屏障疾病的抗VEGF治疗是必不可少的，其中，VEGF是血管异常的主要治疗靶点。
To investigate the mechanism of vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) in Müller cell (MC) viability and neuroprotection in diabetic retinopathy (DR), we examined the role of VEGF in MC viability and BDNF production, and the effect of BDNF on MC viability under diabetic conditions. Mouse primary MCs and cells of a rat MC line, rMC1, were used in investigating MC viability and BDNF production under diabetic conditions. VEGF-stimulated BDNF production was confirmed in mice. The mechanism of BDNF-mediated MC viability was examined using siRNA knockdown. Under diabetic conditions, recombinant VEGF (rVEGF) stimulated MC viability and BDNF production in a dose-dependent manner. rBDNF also supported MC viability in a dose-dependent manner. Targeting BDNF receptor tropomyosin receptor kinase B (TRK-B) with siRNA knockdown substantially downregulated the activated (phosphorylated) form of serine/threonine-specific protein kinase (AKT) and extracellular signal-regulated kinase (ERK), classical survival and proliferation mediators. Finally, the loss of MC viability in TrkB siRNA transfected cells under diabetic conditions was rescued by rBDNF. Our results provide direct evidence that VEGF is a positive regulator for BDNF production in diabetes for the first time. This information is essential for developing BDNF-mediated neuroprotection in DR and hypoxic retinal diseases, and for improving anti-VEGF treatment for these blood–retina barrier disorders, in which VEGF is a major therapeutic target for vascular abnormalities.
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影响因子：
13.7
作者：
Grunwald, Juan E.;Pistilli, Maxwell;Ying, Gui-shuang;Maguire, Maureen G.;Daniel, Ebenezer;Martin, Daniel F.
通讯作者：
Martin, Daniel F.
影响因子：
8.2
作者：
Curtis, T. M.;Hamilton, R.;Stitt, A. W.
通讯作者：
Stitt, A. W.
脂氧化在糖尿病视网膜病变发病机制中的作用
影响因子：
5.2
作者：
Augustine J;Troendle EP;Barabas P;McAleese CA;Friedel T;Stitt AW;Curtis TM
通讯作者：
Curtis TM
影响因子：
12.4
作者：
Almeida, RD;Manadas, BJ;Duarte, CB
通讯作者：
Duarte, CB
低色温双基色发光二极管对三种视网膜细胞的影响
DOI：
10.1016/j.jphotobiol.2020.112099
发表时间：
2021-01-01
影响因子：
5.4
作者：
Jin, Ming;Li, Xiongfeng;Zhang, Xu
通讯作者：
Zhang, Xu