Pathophysiology Section
The spectrum of retinal microvascular lesions which occurs in human diabetic retinopathy is not found in any other ocular or systemic condition or disease in humans (Table 1). The striking degree to which the galactose-fed rat model mimics diabetic retinopathy in humans suggests that a common primary cause is involved in both the hyperglycemia of diabetic patients and the hypergalactosemia of the galactose-fed rat model. The two most likely candidates for a common primary triggering event are increased AR activity and nonenzymatic glycosylation (galactosylation). Galactosemia, like hyperglycemia, causes increases in both. However, the majority of the evidence indicates that increased AR activity and not glycation is the primary event.
= absent or rare; 
= present but not similar to diabetic retinopathy; 
= characteristic of diabetic retinopathy. From Robison, W.G., Jr., Laver, N.M. and Lou, M.F.: The role of aldose reductase in diabetic retinopathy: prevention and intervention studies. p. 593-640. In Osborne, N.N. and Chader, G.J. (Eds.): Progress in Retinal and Eye Research v. 14, Oxford, Pergamon, 1995.
Glycation may be involved in later events of diabetic retinopathy, but this needs to be elucidated. ARI treatment of galactose-fed rats results in 91% and 95% decreases in erythrocyte and retinal galactitol levels, respectively, (Table 2) and ameliorates the diabetic-like retinal microangiopathies, including retinal capillary basement membrane thickening (Figure 8) and the IRMA of the pre-proliferative stages (Figure 9).
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| Figure 8. Prevention of Retinal Capillary Basement Membrane Thickening: Transected retinal capillaries of rats fed 50% galactose for 88 weeks, showing diabetic-like thickening of capillary basement membranes (bm) and diminished size of pericyte (p) compartments in an untreated rat (A) compared to normal basement membrane (bm) thickness and pericyte (p) regions in a galactose-fed rat treated (B) with the aldose reductase inhibitor tolrestat. (Figure 8A: Robison, W.G., Jr. and Nagata, M.: Aldose reductase in mural cell loss and retinal capillary basement membrane thickening, p. 267-275. In Sakamoto, N., Kinoshita, J.H., Kador, P.F. and Hotta, N. (Eds.): Polyol Pathway and Its Role in Diabetic Complications. Amsterdam, Elsevier Science Publishers B.V. (Biomedical Division), 1988); Figure 8B: Kinoshita, J.H., Datiles, M.B., Kador, P.F. and Robison, W.G., Jr.: Aldose reductase and diabetic eye complications. p. 264-278. In Rifkin, H. and Porte, D., Jr. (Eds.): Ellenberg and Rifkin's Diabetes Mellitus: Theory and Practice, Fourth Edition. New York, Elsevier Science Publishing Co., Inc., 1990). |
