Increases in collagen type IV and laminin in galactose-induced retinal capillary basement membrane thickening--prevention by an aldose reductase inhibitor.
Biochemical alterations in the composition of retinal capillary basement membrane components were investigated in galactosemic rats, an animal model that develops basement membrane lesions comparable to those of diabetic retinopathy. Normotensive Wistar-Kyoto rats fed a 30% galactose diet for 9 months developed significant thickening of retinal capillary basement membranes by comparison with animals fed a control test diet (P less than 0.001), or animals on a diet containing 30% galactose and 250 mg kg-1 of the aldose reductase inhibitor sorbinil (P less than 0.001). A quantitative electron microscopic immunogold technique applied on ultrathin sections of the retinas of these animals showed that the labeling densities of collagen type IV and laminin per unit cross-sectional area (which is presumably proportional to the concentrations of these molecules) were significantly increased in the retinal capillary basement membranes of galactose-fed rats, compared with animals on the control test diet. Increases in these two components of basement membranes were prevented by addition of sorbinil to the diet. However, there was no significant change in the labeling density of heparan sulfate proteoglycan (HSPG) core protein in the basement membranes of galactose-fed rats in comparison to animals on either the control diet or galactose-sorbinil diet. Two types of striated fibrillar materials were frequently found in areas of focal thickening of basement membranes of galactose fed rats only. Thinner fibrils reacted strongly with collagen type III antibody, whereas thicker fibrils reacted weakly with collagen type I antibody. Our results indicate that there is an increase in labeling densities of collagen type IV and laminin in thickened basement membranes of retinal capillaries of galactosemic rats along with the expression of interstitial collagens like collagen type III and an abnormal collagen that weakly cross-reacts with antibody to collagen type I, and these effects of galactosemia on the basement membranes are preventable by an aldose reductase inhibitor.
Das
A
A
Kresge Eye Institute, Wayne State University School of Medicine, Detroit, Michigan 48201.
Frank
R N
RN
Zhang
N L
NL
Samadani
E
E
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000517:prevention & control; D005690:Galactose; D005693:Galactosemias / Q000473:pathology; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D007797:Laminin / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY; D012171:Retinal Vessels / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D048289:Imidazolidines; D007797:Laminin; D003094:Collagen; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; C026411:sorbinil; D005690:Galactose