Dark adaptation and hypoxia in diabetic retinopathy

描述（由申请人提供）：糖尿病视网膜病变是美国工作年龄失明的主要原因。然而，导致疾病发展的最初因素仍不清楚。视网膜血管中的血流在糖尿病视网膜病变的早期阶段受到损害。这项拟议的研究将测试这样一种假设，即视网膜血流量的减少，加上夜间视网膜暗适应时发生的视杆细胞光感受器代谢需求的增加，导致视网膜缺氧和糖尿病视网膜病变的发展。这一假设的关键预测尚未得到验证。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）。将通过测量视网膜pO2和确定夜间光暴露以防止视网膜代谢升高是否减缓糖尿病大鼠视网膜病变的进展来检验该假设。该提案的目标是：目标1。测试假设，即在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。将在暗适应和光适应条件下进行测量。目标二。检验夜间暴露于光线以防止视网膜代谢升高减缓糖尿病视网膜病变进展的假设。将通过从诱导糖尿病开始将动物保持在恒定光照下来检验该假设。在主观夜间使用的30勒克斯光水平足够高以使杆系统饱和，但不足以引起光诱导的视网膜损伤。将在诱导糖尿病后0.5、3、6和12个月评估视网膜病变的进展。

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.