Apelin in plasma and vitreous and in fibrovascular retinal membranes of patients with proliferative diabetic retinopathy.

PURPOSE Apelin is an endogenous ligand for the angiotensin-1-like receptor APJ. Because apelin has been reported to regulate angiogenesis, the authors searched for associations between apelin and proliferative diabetic retinopathy. METHODS The study included 55 patients undergoing vitrectomy for proliferative diabetic retinopathy (study group) and 34 patients undergoing vitrectomy for idiopathic preretinal membranes or macular hole (control group). Using enzyme-linked immunosorbent assay, the authors measured the concentrations of apelin and vascular endothelial growth factor (VEGF) in the vitreous and plasma. The expression of apelin and angiotensin-1-like receptor APJ in the excised membranes was examined by fluorescence immunostaining and semiquantitative reverse transcription polymerase chain reaction. RESULTS Vitreous concentrations of apelin were significantly higher in the study group than in the control group (P = 0.005), whereas plasma concentrations of apelin did not vary significantly (P = 0.66). The vitreous concentrations (P < 0.001) and the plasma concentrations (P = 0.03) of VEGF were significantly higher in the study group than in the control group. Neither the vitreous concentrations of apelin and VEGF (P = 0.47) nor the plasma concentrations of apelin and VEGF (P = 0.19) were significantly associated with each other. In the fibrovascular membranes of the study group, colocalization of the endothelial markers CD31 with the markers for apelin and colocalization of the endothelial markers CD31 and APJ was observed. Expression of apelin mRNA (P = 0.03), APJ mRNA (P = 0.02), and VEGF mRNA (P < 0.01) was significantly higher in fibrovascular proliferative diabetic retinopathy membranes than in idiopathic epiretinal membranes. CONCLUSIONS The apelin/APJ system may be involved in retinal neovascularization during the development of proliferative diabetic retinopathy.