Dark adaptation and hypoxia in diabetic retinopathy

糖尿病视网膜病变的暗适应和缺氧

• 批准号: 8474572
• 负责人: ERIC A NEWMAN
• 金额: $ 22.8万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8474572
• 关键词: Age; Albumins; American; Animal Model; Animals; Attention; Blindness; Blood capillaries; Blood flow; Blood-Retinal Barrier; Cell Death; Coupled; Dark Adaptation; Development; Diabetes Mellitus; Diabetic Retinopathy; Disease; Electrodes; Electroretinography; Endothelial Cells; Erythrocytes; Evaluation; Exposure to; Eye; Glial Fibrillary Acidic Protein; Hypoxia; Immunohistochemistry; In Situ Nick-End Labeling; Insulin-Dependent Diabetes Mellitus; Label; Light; Light Adaptations; Masks; Measurement; Measures; Metabolic; Metabolism; Monitor; Neuroglia; Neurons; Optics; Oxygen; Partial Pressure; Patients; Pericytes; Rattus; Research; Research Personnel; Retina; Retinal; Retinal Diseases; Scanning; Sleep; Staging; Staining method; Stains; Streptozocin; Surface; System; Techniques; Testing; Thick; Time; Trypsin; Work; capillary; circadian pacemaker; diabetic rat; novel; prevent; public health relevance; research study; retina blood vessel structure; retinal damage; retinal rods; sensor

DESCRIPTION (provided by applicant): Diabetic retinopathy is the leading cause of blindness in working age Americans. However, the initial factors leading to development of the disease remain unclear. Blood flow in retinal vessels is compromised in early stages of diabetic retinopathy. The proposed research will test the hypothesis that this decrease in retinal blood flow, coupled with the increased metabolic demand of rod photoreceptors that occurs during the night, when the retina is dark-adapted, results in retinal hypoxia and to the development of diabetic retinopathy. Key predictions of this hypothesis remain untested. Notably, retinal pO2 (oxygen partial pressure) has never been directly measured during early stages of diabetic retinopathy. The hypothesis will be tested by measuring retinal pO2 and by determining whether light exposure to prevent elevated retinal metabolism during the night slows the progression of retinopathy in diabetic rats. The aims of the proposal are: Aim 1. Test the hypothesis that elevated retinal metabolism in the dark, coupled with decreased blood flow associated with diabetic retinopathy, results in retinal hypoxia. Retinal blood flow and retinal pO2 will be measured at 0.5, 3, and 6 months following induction of diabetes. Measurements will be made under dark-adapted and light-adapted conditions. Aim 2. Test the hypothesis that light exposure to prevent elevated retinal metabolism at night slows the progression of diabetic retinopathy. This hypothesis will be tested by maintaining animals in constant light from the time diabetes is induced. The 30-lux light level to be used during subjective night is high enough to saturate the rod system but not high enough to cause light-induced retinal damage. The progression of retinopathy will be assessed at 0.5, 3, 6, and 12 months following induction of diabetes.

描述（由申请人提供）：糖尿病视网膜病变是美国工作年龄人口失明的主要原因。然而，导致该疾病发生的最初因素仍不清楚。在糖尿病视网膜病变的早期阶段，视网膜血管的血流受到损害。拟议的研究将检验这样的假设：视网膜血流量的减少，加上夜间视网膜暗适应时杆状光感受器代谢需求的增加，导致视网膜缺氧并导致糖尿病视网膜病变的发展。这一假设的关键预测尚未得到检验。值得注意的是，在糖尿病视网膜病变的早期阶段从未直接测量过视网膜 pO2（氧分压）。该假设将通过测量视网膜 pO2 并确定夜间暴露在光线下以防止视网膜代谢升高是否会减缓糖尿病大鼠视网膜病变的进展来进行检验。该提案的目的是： 目标 1. 检验以下假设：黑暗中视网膜代谢升高，加上与糖尿病视网膜病变相关的血流量减少，导致视网膜缺氧。将在诱导糖尿病后 0.5、3 和 6 个月测量视网膜血流量和视网膜 pO2。测量将在暗适应和光适应条件下进行。目标 2. 检验以下假设：通过光照来防止夜间视网膜代谢升高可减缓糖尿病视网膜病变的进展。这一假设将通过从诱发糖尿病时起使动物保持在恒定光照下来进行检验。主观夜间使用的 30 勒克斯光照水平足以使视杆系统饱和，但又不足以导致光引起的视网膜损伤。将在诱发糖尿病后 0.5、3、6 和 12 个月评估视网膜病变的进展情况。