ALTERED PROLIFERATION OF RETINAL MICROVASCULAR CELLS ON GLYCATED MATRIX

Purpose. To investigate the effect of nonenzymatic glycosylation (glyc ation) of basement membranes (BM) and isolated BM proteins on the grow th of retinal pericytes and retinal endothelial cells. Methods. Type I V collagen, laminin, Engelbreth-Holm-Swarm tumor basement membrane (EH S-BM) and bovine retinal basement membrane (RBM), after incubation in the presence of reducing sugars to induce glucose-mediated modificatio ns, or in the absence of any sugar (control), were used as a substrate to culture bovine retinal microvascular cells. Cell growth on the non enzymatically glycosylated and the corresponding control substrates wa s measured daily, using an automated cell counter. Results, Retinal pe ricytes seeded on glycated type IV collagen proliferated consistently more slowly than on control type TV collagen (P= 0.02), showing a 20% to 33% decrease throughout most of the growth curve, whereas on glycat ed laminin the difference from control was not significant. In contras t, proliferation increased by 16% to 25% for retinal endothelial cells on glycated laminin compared with control substrate (P = 0.025), wher eas on glycated type IV collagen the growth curve was not significantl y different from the curve for the control. When seeded on whole glyca ted EHS-BM or RBM, proliferation of pericytes decreased by 20% to 30% (P = 0.04); the endothelial cells showed no difference on glycated EHS -BM, however, the growth rate increased on glycated RBM by 25% to 30% more than it did for the control (P = 0.01). Conclusions. Nonenzymatic glycosylation of intact BM or individual BM macromolecules resulted i n reduced proliferation of retinal pericytces and increased proliferat ion of retinal endothelial cells. These in vitro observations resemble some of the pathologic changes of the retinal microvascular cells obs erved in situ, when diabetic retinopathy develops.