Purpose: Apelin, a novel cytokine, was reported to regulate angiogenesis. The aim of this study was to investigate the correlation between apelin and retinopathy of prematurity (ROP), between apelin and the other known angiogenic cytokines including vascular endothelial growth factor (VEGF) and hypoxia-induced factor-1a (HIF-1a).

Methods: The study included 36 ROP patients who underwent vitrectomy. Previous intravitreal bevacizumab (IVB) was performed in 18 patients (IVB group). The other ROP eyes belonged to non-IVB group. Surgical removed membranes from 10 patients who underwent vitrectomy for idiopathic preretinal membranes or macular hole served as control. The expression of apelin and angiotensin-1-like receptor (APJ) in the excised membranes was examined by fluorescence immunostaining. Quantitative reverse transcription polymerase chain reaction was used to examine the expression of apelin, VEGF, and HIF-1a mRNA.

Results: The density of neovascularization in fibrovascular membranes was significantly correlated with the age and postconception age of ROP patients (r = -0.94, P < 0.01; r = -0.83, P = 0.04). In the non-IVB group, colocalization of the endothelial marker CD31 with the marker for apelin and colocalization of CD31 and APJ were observed. In the IVB group, staining of apelin and APJ were positive, whereas the staining of CD31 was negative. Expression of apelin mRNA, HIF-1a mRNA, and VEGF mRNA were significantly higher in ROP membranes than idiopathic epiretinal membranes. Expression of apelin mRNA and VEGF mRNA significantly correlate with HIF-1a mRNA (r = 0.64, P = 0.04; and r = 0.96, P < 0.01, respectively), but the expression of apelin mRNA did not significantly correlate with VEGF mRNA (r = 0.491, P = 0.15).

Conclusion: The apelin/APJ system may be involved in the development of retinal neovascularization of ROP. The present results showed that the effect of apelin was related to HIF-1a but independent with VEGF. RETINA 33:613-620, 2013