Detection of Vascular Endothelial Growth Factor and Tumor Necrosis Factor Alpha in Epiretinal Membranes of Proliferative Diabetic Retinopathy, Proliferative Vitreoretinopathy and Macular Pucker

Abstract

Purpose: To evaluate epiretinal membranes in proliferative eye disease for the presence of vascular endothelial growth factor (VEGF) and tumor necrosis factor α (TNF-α). Methods: Membranes were surgically removed from 66 patients with proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR) and macular pucker (MP). Cytokine concentrations were determined by ELISA (VEGF) and bioassay (TNF-α). Results: VEGF was detected in all 66 membranes investigated. The highest VEGF values were found in patients with type I diabetes (mean = 5,994 pg/mg protein). In patients with type II diabetes, the values were at a mean of 1,242 pg/mg protein. When coagulation therapy was performed for longer than 3 months prior to surgery, VEGF was significantly (p < 0.05) reduced. Intermediate levels of VEGF were found in PVR membranes (mean = 1,417 pg/mg protein). The lowest activity was found in MP (mean = 216 pg/mg protein). In contrast, TNF-α was present in 16 PDR membranes, 9 PVR membranes and 8 MP membranes. Conclusion: The presence of VEGF in all membranes investigated indicates that this cytokine plays an important role in angiogenesis in ischemic retinal disease and in membrane growth in proliferative disorders.

Thrombin Regulates Chemokine Induction during Human Retinal Pigment Epithelial Cell/Monocyte Interaction

“…They have been identified on epiretinal membranes removed surgically from patients with proliferative vitreoretinopathy and on epiretinal membranes produced experimentally. 39,40 In this study, thrombin generally potentiated exogenous IL-1␤-and TNF-␣-induced IL-8, MCP-1, and IL-6 production by HRPE cells, monocytes, and HRPE cell/monocyte co-cultures. Synergistic effects of thrombin and IL-1␤ on IL-8 production by HRPE cell/ monocyte co-cultures were particularly prominent.…”

Alterations of the Rat Mesentery Vasculature in Experimental Diabetes

“…80, No. 8, p. 1171 Copyright © 2000 of this cytokine appears be stimulated by local ischemia (Armstrong et al, 1998) or by general factors such as high concentrations of glucose (Natarajan et al, 1997) and advanced glycation end products (Hirata et al, 1997). The question addressed in this paper is whether vascular beds other than those generally known to be affected by diabetes (eye, kidney, and nerves) are also susceptible to alteration by this disease.…”

“…This abnormal endothelial proliferation is at present explained by the expression, at the affected site, of endothelial growth factors, particularly the vascular endothelial growth factor (VEGF). Synthesis of this cytokine appears be stimulated by local ischemia (Armstrong et al, 1998) or by general factors such as high concentrations of glucose (Natarajan et al, 1997) and advanced glycation end products (Hirata et al, 1997).…”

Clinical validation of a link between TNF-α and the glycosylation enzyme core 2 GlcNAc-T and the relationship of this link to diabetic retinopathy

“…In this regard, leucocytes of CD18 and ICAM-1 knock-out mice exhibited significantly decreased adhesion properties, which was associated with fewer damaged endothelial cells and less vascular leakage [27]. The contribution of TNF-α to the onset and progression of diabetic retinopathy is clearly supported by a number of previous studies [28][29][30][31][32][33][34], suggesting the therapeutic potential of anti-inflammatory treatments.…”