VEGF as a Direct Functional Regulator of Photoreceptors and Contributing Factor to Diabetes-Induced Alteration of Photoreceptor Function.
VEGF as a Direct Functional Regulator of Photoreceptors and Contributing Factor to Diabetes-Induced Alteration of Photoreceptor Function.
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DOI：
10.3390/biom11070988
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发表时间：
2021-07-05
期刊：
影响因子：
5.5
通讯作者：
Le YZ
中科院分区：
文献类型：
--
作者：
Hu J;Zhu M;Li D;Wu Q;Le YZ
血管内皮生长因子（VEGF）是糖尿病视网膜病变（DR）、年龄相关性黄斑变性（AMD）和其他缺氧性视网膜血管疾病中血视网膜屏障（BRB）破坏的主要治疗靶点。为了确定VEGF是否是视网膜神经元功能的直接调节剂及其在DR进展过程中改变视力的潜在作用，我们在C57 BL 6背景野生型（WT）和秋田自发性糖尿病小鼠中用视网膜电图检查了重组VEGF（rVEGF）对光感受器功能的直接影响。玻璃体内注射后不久，rVEGF以剂量依赖性方式导致暗适应1.5月龄WT小鼠的暗视ERG a波和b波振幅以及明视ERG b波振幅显着降低。与WT对照组相比，5月龄秋田自发性糖尿病小鼠表现出暗视ERG a波和b波振幅以及明视ERG b波振幅显著降低。然而，在野生型对照组中，rVEGF改变光感受器功能的作用在5月龄秋田自发性糖尿病小鼠中减弱。总之，我们的研究结果表明，血管内皮生长因子是一个直接的光感受器的功能调节和血管内皮生长因子在DR的上调是糖尿病引起的光感受器功能的改变的一个因素。这些信息对于了解DR、AMD和其他缺氧性视网膜血管疾病中BRB分解的治疗效果以及抗VEGF药物治疗患者的护理至关重要。
Vascular endothelial growth factor (VEGF) is a major therapeutic target for blood–retina barrier (BRB) breakdown in diabetic retinopathy (DR), age-related macular degeneration (AMD), and other hypoxic retinal vascular disorders. To determine whether VEGF is a direct regulator of retinal neuronal function and its potential role in altering vision during the progression of DR, we examined the immediate impact of recombinant VEGF (rVEGF) on photoreceptor function with electroretinography in C57BL6 background wild-type (WT) and Akita spontaneous diabetic mice. Shortly after intravitreal injections, rVEGF caused a significant reduction of scotopic ERG a-wave and b-wave amplitudes and photopic ERG b-wave amplitudes in a dose-dependent manner in dark-adapted 1.5-mo-old WT mice. Compared with WT controls, 5-mo-old Akita spontaneous diabetic mice demonstrated a significant reduction in scotopic ERG a-wave and b-wave amplitudes and photopic ERG b-wave amplitudes. However, the effect of rVEGF altered photoreceptor function in WT controls was diminished in 5-mo-old Akita spontaneous diabetic mice. In conclusion, our results suggest that VEGF is a direct functional regulator of photoreceptors and VEGF up-regulation in DR is a contributing factor to diabetes-induced alteration of photoreceptor function. This information is critical to the understanding of the therapeutic effect and to the care of anti-VEGF drug-treated patients for BRB breakdown in DR, AMD, and other hypoxic retinal vascular disorders.
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DOI：
10.1016/j.ajpath.2017.06.007
发表时间：
2017-10
期刊：
The American journal of pathology
影响因子：
--
作者：
Malechka VV;Moiseyev G;Takahashi Y;Shin Y;Ma JX
通讯作者：
Ma JX
影响因子：
15.9
作者：
Barber, AJ;Lieth, E;Gardner, TW
通讯作者：
Gardner, TW
影响因子：
3.7
作者：
Saint-Geniez M;Maharaj AS;Walshe TE;Tucker BA;Sekiyama E;Kurihara T;Darland DC;Young MJ;D'Amore PA
通讯作者：
D'Amore PA
影响因子：
4.4
作者：
McGill, Trevor J.;Prusky, Glen T.;LaVail, Matthew M.
通讯作者：
LaVail, Matthew M.
影响因子：
15.9
作者：
Shih, SC;Ju, MH;Smith, LEH
通讯作者：
Smith, LEH