Department of Medicine/Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Department of Ophthalmology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Adv Exp Med Biol. 2023;1415:487-491. doi: 10.1007/978-3-031-27681-1_71.
Vascular endothelial growth factor (VEGF or VEGF-A), a major pathogenic factor for diabetic and hypoxic blood-retina barrier (BRB) diseases, has been shown to act as a direct functional regulator for neurons in the peripheral and central nerve systems. To determine if VEGF plays a direct role in regulating retinal neuronal function, we established specific experimental procedures and examined the effect of recombinant VEGF (rVEGF) on photoreceptor function with electroretinography (ERG) in mice. In our case, 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 wild-type (WT) mice, shortly after the intravitreal delivery of rVEGF in dark. However, the effect of rVEGF on photoreceptor function was nullified in adult Akita diabetic mice. Our data strongly suggest that VEGF is a direct regulator of photoreceptor function and VEGF upregulation contributes significantly to the diabetes-induced reduction of photoreceptor function. In this chapter, we will discuss the relevant background, key experimental procedures and results, and clinical significance of our work.
血管内皮生长因子(VEGF 或 VEGF-A)是糖尿病和缺氧性血视网膜屏障(BRB)疾病的主要致病因子,已被证明可作为周围和中枢神经系统神经元的直接功能调节剂。为了确定 VEGF 是否在调节视网膜神经元功能中发挥直接作用,我们建立了特定的实验程序,并通过视网膜电图(ERG)检查重组 VEGF(rVEGF)对暗适应野生型(WT)小鼠中光感受器功能的影响。在我们的案例中,rVEGF 在暗适应后玻璃体腔内注射 rVEGF 后不久,以剂量依赖性方式导致暗适应 WT 小鼠的暗视 ERG a 波和 b 波幅度以及明视 ERG b 波幅度显著降低。然而,rVEGF 对光感受器功能的影响在成年 Akita 糖尿病小鼠中被消除。我们的数据强烈表明,VEGF 是光感受器功能的直接调节剂,VEGF 的上调对糖尿病诱导的光感受器功能下降有重要贡献。在这一章中,我们将讨论我们工作的相关背景、关键实验程序和结果以及临床意义。