Departments of Physiology Biomedical Engineering, University of Arizona, Tucson, Arizona.
Department of Biomedical Engineering, University of Arizona, Tucson, Arizona.
Vis Neurosci. 2020 Sep 16;37:E006. doi: 10.1017/S095252382000005X.
Diabetic retinopathy is now well understood as a neurovascular disease. Significant deficits early in diabetes are found in the inner retina that consists of bipolar cells that receive inputs from rod and cone photoreceptors, ganglion cells that receive inputs from bipolar cells, and amacrine cells that modulate these connections. These functional deficits can be measured in vivo in diabetic humans and animal models using the electroretinogram (ERG) and behavioral visual testing. Early effects of diabetes on both the human and animal model ERGs are changes to the oscillatory potentials that suggest dysfunctional communication between amacrine cells and bipolar cells as well as ERG measures that suggest ganglion cell dysfunction. These are coupled with changes in contrast sensitivity that suggest inner retinal changes. Mechanistic in vitro neuronal studies have suggested that these inner retinal changes are due to decreased inhibition in the retina, potentially due to decreased gamma aminobutyric acid (GABA) release, increased glutamate release, and increased excitation of retinal ganglion cells. Inner retinal deficits in dopamine levels have also been observed that can be reversed to limit inner retinal damage. Inner retinal targets present a promising new avenue for therapies for early-stage diabetic eye disease.
糖尿病性视网膜病变现在被认为是一种神经血管疾病。在糖尿病的早期，内视网膜就会出现明显的缺陷，内视网膜由接收来自视杆和视锥光感受器的输入的双极细胞、接收来自双极细胞的输入的神经节细胞以及调节这些连接的无长突细胞组成。这些功能缺陷可以在糖尿病患者和动物模型中通过视网膜电图 (ERG) 和行为视觉测试在体内进行测量。糖尿病对人和动物模型 ERG 的早期影响是振荡电位的变化，表明无长突细胞和双极细胞之间的通信功能障碍，以及 ERG 测量表明神经节细胞功能障碍。这与对比度敏感性的变化相关联，表明内视网膜发生了变化。体外神经元机制研究表明，这些内视网膜变化是由于视网膜抑制作用降低引起的，可能是由于 GABA 释放减少、谷氨酸释放增加以及视网膜神经节细胞兴奋增加所致。还观察到多巴胺水平在内视网膜中的降低，这可以通过逆转来限制内视网膜损伤。内视网膜靶标为早期糖尿病眼病的治疗提供了一个有前途的新途径。
