Diabetes-related histopathologies of the rat retina prevented with an aldose reductase inhibitor.
Recent evidence obtained from both galactosemic dogs and rats indicated that aldose reductase inhibitors could prevent several capillary lesions which were similar to those typical of diabetic retinopathy in humans. The present study demonstrates that diabetes-like histopathological changes in the intact retina, which were not visible in the vessel whole mounts used previously, can also be prevented. Sprague-Dawley rats were fed diets containing 50% galactose with or without an aldose reductase inhibitor (tolrestat). After 28 months of galactose feeding, the findings from retinal transections examined by light and electron microscopy were consistent with reports on vessel whole mounts, but showed several additional changes. There was a marked increase in the thickness of the retinal inner limiting membrane, as well as in the capillary basement membranes. There was extensive gliosis and disruption of retinal layers as well as pericyte degeneration, endothelial cell proliferation, accellularity, capillary dilation, and microaneurysm formation. The contents of pericyte compartments in the capillary wall were often replaced with non-pericyte cytoplasm, which appeared glial cell-like. Many of the lumens of acellular capillaries were occluded with debris from degenerating endothelial cells or with cytoplasm possibly originating from glial cell processes. Structures suggestive of degenerated microaneurysms were present mainly in the inner nuclear and outer plexiform layers. The microaneurysms and other major changes were limited to the central and paracentral retina. All these retinal lesions were prevented with orally administered tolrestat. Thus, long-term galactosemia in rats induced histopathologically visible angiopathies, simulating those occurring in background diabetic retinopathy in humans, and these were prevented by treatment with an aldose reductase inhibitor.
Robison
W G
WG
National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
Tillis
T N
TN
Laver
N
N
Kinoshita
J H
JH
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000502:physiology; D000818:Animals; D001485:Basement Membrane / Q000648:ultrastructure; D002196:Capillaries / Q000648:ultrastructure; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003930:Diabetic Retinopathy / Q000473:pathology / Q000517:prevention & control; D005260:Female; D005690:Galactose; D008854:Microscopy, Electron; D009281:Naphthalenes / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000648:ultrastructure*; D012171:Retinal Vessels / Q000648:ultrastructure; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D009281:Naphthalenes; C040550:tolrestat; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; D005690:Galactose