Diabetic retinopathy remains a leading cause of blindness in young people in this country despite recombinant human insulin, insulin pumps, pancreas transplantation, and laser and vitreous surgery. Also, we do not yet know the initial event which leads to retinal vascular cell dysfunction, or the mechanism of cell injury. Insulin regulates numerous cell functions, including sodium-potassium ATPase (sodium pump) activity in nonvascular cells. Diabetes reduces sodium pump activity in vascular and neural tissues. We hypothesize that deficient insulin action is the initial event which leads to diabetic retinopathy via its effect on endothelial cell sodium-potassium ATPase. In this project we will examine the effects of deficient insulin action and excess glucose on isoform-specific activity and expression of the sodium pump, as well as on cell volume, free cytosolic calcium content, and permeability in cultures of bovine retinal endothelial cells. These in vitro studies will help to determine the specific initial event, and to characterize one mechanism of cellular injury in diabetes. We will also determine the effects of diabetes on retinal vascular sodium pump protein content in rats and humans. These in vivo studies will help to define the role of the sodium pump in the pathogenesis of diabetic retinopathy. Collectively, this work will provide important new understanding of the molecular and cellular pathogenesis of diabetic retinopathy, and pave the way for future means to prevent vascular cell damage in diabetes.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Physician Scientist Award (K11)
Project #
5K11EY000331-03
Application #
2157827
Study Section
Vision Research and Training Committee (VSN)
Project Start
1993-01-01
Project End
1997-12-31
Budget Start
1995-01-01
Budget End
1995-12-31
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033