Retinal neovascularization characterizes proliferative diabetic retinopathy (PDR). Pigment epithelium-derived factor (PEDF) has been shown to be a major antiangiogenic growth factor in the mammalian eye. PEDF expression is suppressed by hypoxia, and changes in PEDF have been correlated to the development of retinal neovascularization in animal models of hypoxic eye disease. However, whether this concept of a reduced angiogenesis inhibitor holds true in humans is as yet unclear. In this study, we analyzed the in vivo regulation of PEDF in patients with and without hypoxic eye disease. We used immunoblots to measure PEDF in ocular fluids obtained from 64 nondiabetic and diabetic patients. In addition, immunohistochemistry of PEDF was carried out in specimens of normal human retinas and retinas with various degrees of diabetic retinopathy. The PEDF concentrations in patients with PDR (P < 0.001) or extensive nondiabetic retinal neovascularization caused by retinal-vein occlusion (P < 0.001) were lower than in control patients. Levels of PEDF were replenished in PDR patients with previous retinal scatter photocoagulation compared with PDR patients without previous photocoagulation (P ‫؍‬ 0.01). Immunohistochemistry revealed an interstitial staining pattern as expected for a secreted protein, with an intense staining in retinas of patients without proliferative eye disease. However, in patients with PDR, little or no staining was detectable. Our data strongly support the concept that retinal angiogenesis is induced by loss of the major angiogenesis inhibitor in the eye, PEDF, in combination with an increased expression of angiogenic growth factors such as vascular endothelial growth factor. Our findings suggest that substitution of angiogenesis inhibitors may be an effective approach in the treatment of PDR. Diabetes 50: [2641][2642][2643][2644][2645] 2001 T he control of retinal angiogenesis is of critical importance for the preservation of vision. Retinal neovascularization characterizes proliferative diabetic retinopathy (PDR), which is still one of the most common causes of blindness worldwide. Retinal ischemia induces intraocular neovascularization, presumably by stimulating the expression of angiogenic growth factors and by inhibiting the release of antiangiogenic cytokines (1,2). Vitreal levels of angiogenic growth factors have been shown to be directly associated with the degree of retinal angiogenesis (3,4). The ability to monitor and grade retinal angiogenesis within the eye as well as the ability to aspirate vitreous, which is known to contain retina-derived growth factors in direct association to the stage of retinal angiogenesis, makes the eye an ideal setting in which to investigate the delicate balance of new vessel growth and the influence of specific growth factors in vivo in humans.Pigment epithelium-derived factor (PEDF) protects cerebellar granule cells against neurotoxic agents (5) and is also called early population doubling level cDNA-1 (EPC-1), reflecting its upregulation during cell cycle ...

Isoflavones have beneficial effects on CRP concentrations, but not on other inflammatory biomarkers of cardiovascular disease risk in postmenopausal women, and may improve VCAM-1 in an ERbeta gene polymorphic subgroup.