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.

Public Health Relevance

Diabetic retinopathy is the leading cause of blindness in working age Americans. The proposed research will test the hypothesis that the disease is caused by retinal hypoxia due to decreased blood flow and the high metabolic demand of rod photoreceptors in the dark. If the hypothesis proves correct, a simple and inexpensive therapy, having diabetes patients wear illuminated masks to light adapt their eyes while they sleep, might prove effective in slowing or preventing the development of retinopathy.

Agency
National Institute of Health (NIH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21EY023216-02
Application #
8623133
Study Section
(DPVS)
Program Officer
Shen, Grace L
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Neurosciences
Type
Schools of Medicine
DUNS #
City
Minneapolis
State
MN
Country
United States
Zip Code
55455