Abstract
Abstract: :
Purpose: To characterize platelet density changes in the retinae of STZ-induced diabetic rats and the effects of Fas/FasL blockade. Methods: Diabetes was induced with streptozotocin (STZ) in Long Evans rats. At 1, 2, and 4 weeks after STZ administration, platelets were collected from donor rats, labeled with CFDASE, and injected into the tail vein of recipient rats. The fundi were examined by scanning laser ophthalmoscope (SLO) 24 hours later. Neutralizing antibodies against rat FasL were administered intraperitoneally 2 days before platelet injection so as to investigate the effect of blocking leukocyte-induced Fas/FasL endothelial apoptosis on platelet accumulation. Results: Retinal platelet density was significantly elevated at 2 weeks (n = 12, p < 0.01) compared to non-diabetic rats (n = 14). A three-fold increase in retinal platelet density was seen at four weeks (n = 7, p < 0.01). The diabetes induced platelet density increases were maximized when diabetic platelets were infused into diabetic animals, while platelet density did not increase when diabetic platelets were infused into non-diabetic animals, or non-diabetic platelets were infused into diabetic animals. The administration of neutralizing anti-FasL antibodies significantly suppressed the diabetes-induced increases in retinal platelet density (n = 10, p < 0.01). Conclusion: The density of platelets in the retinal vasculature increases within two weeks of diabetes onset. The increased platelet density is maximized when diabetic platelets and a diabetic endothelium are present. The platelet density increases are likely secondary to Fas/FasL-induced endothelial cell apoptosis.
Keywords: 388 diabetic retinopathy • 323 apoptosis/cell death • 339 cell adhesions/cell junctions