We are continuing our studies to attempt to develop a model of diabetic retinopathy in rats made diabetic with streptozotocin, and in addition to investigate other aspects of the pathologic anatomy and physiology of other tissues in the eyes, brains, and other organs of these animals. In addition to diabetes, other conditions are superimposed in our attempt to promote the development of retinopathy. These include systemic hypertension in a strain of rat in which this is a genetic lesion, and diets high in sucrose. The role of aldose reductase is investigated by observing the effects of the drug CP-45634, an inhibitor of this enzyme and by feeding some animals diets rich in galactose. The role of diabetes is investigated by use of insulin therapy in some animals. After one year on these regimens, animals are sacrificed, and flat mounts of the retinal vessels are prepared by trypsin digestion. The anatomical configuration and permeability of the retinal vessels and of the retinal pigment epithelium are investigated by electron microscopy using the tracers horseradish peroxidase and microperoxidase. In addition, we will examine by light and scanning and transmission electron microscopy cerebral vessels, sciatic nerves and kidneys of animals on the various regimens. Observations will be recorded by several individuals who are masked as to the identities of the experimental animals to avoid bias. In this way, we can objectively determine what abnormalities are present that are related to diabetes.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY002566-08
Application #
3256857
Study Section
(VID)
Project Start
1978-09-01
Project End
1986-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
8
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Wayne State University
Department
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
Frank, R N; Amin, R H; Puklin, J E (1999) Antioxidant enzymes in the macular retinal pigment epithelium of eyes with neovascular age-related macular degeneration. Am J Ophthalmol 127:694-709
Frank, R N (1998) ""Oxidative protector"" enzymes in the macular retinal pigment epithelium of aging eyes and eyes with age-related macular degeneration. Trans Am Ophthalmol Soc 96:635-89
Amin, R H; Frank, R N; Kennedy, A et al. (1997) Vascular endothelial growth factor is present in glial cells of the retina and optic nerve of human subjects with nonproliferative diabetic retinopathy. Invest Ophthalmol Vis Sci 38:36-47
Frank, R N; Amin, R; Kennedy, A et al. (1997) An aldose reductase inhibitor and aminoguanidine prevent vascular endothelial growth factor expression in rats with long-term galactosemia. Arch Ophthalmol 115:1036-47
Frank, R N (1997) Growth factors in age-related macular degeneration: pathogenic and therapeutic implications. Ophthalmic Res 29:341-53
Frank, R N; Amin, R H; Eliott, D et al. (1996) Basic fibroblast growth factor and vascular endothelial growth factor are present in epiretinal and choroidal neovascular membranes. Am J Ophthalmol 122:393-403
Amin, R; Puklin, J E; Frank, R N (1994) Growth factor localization in choroidal neovascular membranes of age-related macular degeneration. Invest Ophthalmol Vis Sci 35:3178-88
Frank, R N (1994) The aldose reductase controversy. Diabetes 43:169-72
Das, A; Puklin, J E; Frank, R N et al. (1992) Ultrastructural immunocytochemistry of subretinal neovascular membranes in age-related macular degeneration. Ophthalmology 99:1368-76
Frank, R N (1991) On the pathogenesis of diabetic retinopathy. A 1990 update. Ophthalmology 98:586-93

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