Expression of thrombospondin-2 as a marker in proliferative diabetic retinopathy

Purpose: To determine the expression of the endogenous anti-angiogenic and pro-fibrotic matricellular protein thrombospondin (TSP)-2 and its receptors CD36 and CD47 in proliferative diabetic retinopathy (PDR). In addition, we examined the expression of TSP-2 in the retinas of diabetic rats. Methods: Epiretinal membranes from 14 patients with PDR and nine patients with proliferative vitreoretinopathy were studied by immunohistochemistry. Vitreous samples from 30 PDR and 25 nondiabetic patients were studied by enzyme-linked immunosorbent assay. Vitreous samples and retinas of rats were examined by Western blotting. Results: In epiretinal membranes, vascular endothelial cells and myofibroblasts expressed TSP-2, CD36 and CD47. In PDR membranes, significant correlations were observed between numbers of blood vessels expressing the panendothelial cell marker CD34 and numbers of blood vessels and stromal cells expressing TSP-2, CD36 and CD47. The numbers of blood vessels and stromal cells expressing CD34, TSP-2, CD36 and CD47 were significantly higher in membranes with active neovascularization when compared with those with quiescent disease. Thrombospondin-2 levels in vitreous samples from PDR patients were significantly higher than those in control patients without diabetes (p < 0.001). Western blot analysis revealed a significant increase in the expression of intact and cleaved TSP-2 in vitreous samples from PDR patients and in the retinas of diabetic rats compared to nondiabetic controls. Conclusions: Upregulation of TSP-2 may be a protective mechanism against inflammation and angiogenesis associated with PDR.