Das A, Frank R N, Zhang N L, Samadani E
Kresge Eye Institute, Wayne State University School of Medicine, Detroit, Michigan 48201.
Exp Eye Res. 1990 Mar;50(3):269-80. doi: 10.1016/0014-4835(90)90211-c.
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.
在半乳糖血症大鼠中研究了视网膜毛细血管基底膜成分的生化改变，半乳糖血症大鼠是一种动物模型，其发生的基底膜病变与糖尿病视网膜病变相似。与喂食对照试验饮食的动物（P<0.001）或喂食含30%半乳糖和250mg/kg醛糖还原酶抑制剂索比尼尔饮食的动物（P<0.001）相比，血压正常的Wistar-Kyoto大鼠喂食30%半乳糖饮食9个月后，视网膜毛细血管基底膜显著增厚。应用定量电子显微镜免疫金技术对这些动物视网膜的超薄切片进行检测，结果显示，与喂食对照试验饮食的动物相比，喂食半乳糖的大鼠视网膜毛细血管基底膜中每单位横截面积的IV型胶原和层粘连蛋白的标记密度（推测与这些分子的浓度成正比）显著增加。向饮食中添加索比尼尔可防止基底膜这两种成分的增加。然而，与喂食对照饮食或半乳糖-索比尼尔饮食的动物相比，喂食半乳糖的大鼠基底膜中硫酸乙酰肝素蛋白聚糖（HSPG）核心蛋白的标记密度没有显著变化。仅在喂食半乳糖的大鼠基底膜局灶性增厚区域经常发现两种类型的横纹纤维状物质。较细的纤维与III型胶原抗体反应强烈，而较粗的纤维与I型胶原抗体反应较弱。我们的结果表明，半乳糖血症大鼠视网膜毛细血管增厚的基底膜中IV型胶原和层粘连蛋白的标记密度增加，同时伴有III型胶原等间质胶原的表达以及与I型胶原抗体弱交叉反应的异常胶原的表达，半乳糖血症对基底膜的这些影响可被醛糖还原酶抑制剂预防。
