Dogs fed galactose diet develop retinal capillary changes that are similar to human diabetic retinopathy. This animal model develops not only early capillary changes such as microaneurysms and various sizes of retinal hemorrhages but also the advanced stage of proliferative changes where new vessels grow into vitreous body. This indicates that, like human retinopathy, the occlusion of retinal capillaries underlie the development of retinal changes in galactose-fed dogs. To understand the mechanism of capillary occlusion, which initiates these retinal lesions, our research has been focussed on the interaction of retinal capillary cells and leukocytes. Dogs placed on 30% galactose diet displayed both lymphocyte and neutrophil dysfunction. Blastformation induced by lectins of lymphocytes isolated from galactose-fed dogs was significantly lower than that of non-galactosemic control dogs. Although many neutrophil functions such as chemotaxis were in the normal range, induction of NADPH oxidase was decreased in galactose-fed dogs. Dog neutrophils undergo apoptosis by various stimulants such as TNF-alpha, PMA and cycloheximide. Apoptosis induced by these three stimulants was significantly suppressed in galactose-fed dogs. Despite the apparent suppression of apoptosis, neutrophils isolated from galactose-fed dogs demonstrated a dramatically increased interaction with retinal capillary endothelial cells. Since a higher incidence of infection occurs in patients with diabetes and the reaction to various inflammations tends to be more severe in diabetics than non-diabetics, the increased interaction of activated neutrophils may either initiate or accelerate capillary occlusion observed in diabetic retinopathy.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Intramural Research (Z01)
Project #
1Z01EY000275-06
Application #
6162371
Study Section
Special Emphasis Panel ( LOT)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1997
Total Cost
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code