Modulation of thrombospondin 1 and pigment epithelium-derived factor levels in vitreous fluid of patients with diabetes.

OBJECTIVE To determine the levels of 2 endogenous inhibitors of angiogenesis, thrombospondin 1 (TSP-1) and pigment epithelium-derived factor (PEDF), in the vitreous fluid from patients with and without diabetes. METHODS The levels of TSP-1 and PEDF in vitreous samples from diabetic and age-matched nondiabetic patients were determined by Western blot analysis. RESULTS We observed significant amounts of TSP-1 and PEDF in the vitreous samples of control eyes. The TSP-1 levels varied in samples from patients with diabetes. In contrast, PEDF levels showed little or no change in vitreous samples from patients with or without diabetes. However, the PEDF protein exhibited variation in its molecular weight among the samples. We consistently observed lower levels of TSP-1 in diabetic patients who expressed the higher-molecular-weight PEDF isoform. CONCLUSIONS In diabetes, changes in the TSP-1 level may play a role in shifting the angiogenic balance and contributing to the pathogenesis of diabetic retinopathy. Although the PEDF level did not change, the diabetic samples with the higher-molecular-weight PEDF isoform consistently showed lower levels of TSP-1. CLINICAL RELEVANCE The presence of the higher-molecular-weight PEDF isoform may be associated with greater risk of severe diabetic retinopathy.