Objective To investigate the inhibitory effects of 5-lipoxygenase (5-LOX) on oxygen-induced retinal neovascularization in mice and to explore its possible mechanisms. Methods 7-day-old C57BL/6J mice were randomly divided into normal group, oxygen induced retinopathy (OIR) model group, large-dose group, small-dose group and control group with 12 mice in each group. The mice with their mothers were kept in (75±2)% of oxygen environment for 5 days and then returned to normoxia for 5 days to establish the OIR model except for normal group. From postnatal day 12 to 17, the large-dose group and small-dose group received intravitreous injection of 5-LOX at dose of 100 mg/kg and 50 mg/kg respectively, while the control group received the same volume of 1% dimethyl sulfoxide. The mice in the OIR group received no treatment. The number of endothelium cell nuclei breaking through the inner limiting membrane (ILM) was counted on hematoxylin and eosin-stained retinal section. The mRNA expression of 5-LOX, vascular endothelial growth factor (VEGF)-a, VEGF receptor 2 (VEGFR-2) on retinal tissue were detected by reverse transcription polymerase chain reaction (RT-PCR). The protein expression of 5-LOX, VEGF-a, VEGFR-2 and phosphorylation extracellular signal-regulated kinase (P-ERK) 1/2 on retinal tissue were detected by Western blot. Results The number of vascular cell nuclei breaking through the ILM in the large-dose group and small-dose group decreased significantly compared with the OIR group and control group (F=73.390, P < 0.05). The mRNA expression and protein expression of 5-LOX, VEGFa, VEGFR-2 on retinal tissue were decreased significantly in the large-dose group and small-dose group as compared with the OIR group and control group (F=92.668, P < 0.05). The difference of VEGFR-2 protein expression between large-dose group and small-dose group was not significant (F=2.118, P > 0.05). The differences of 5-LOX, VEGF-a, P-ERK 1/2 protein expression between large-dose group and small-dose group were significant (F=86.490, 165.128, 139.424; P < 0.05). Conclusion Hypoxia may induce 5-LOX expression in the retina. Retinal neovascularization was significantly inhibited by selective inhibition of 5-LOX.

Citation： HeTao, JiangLi, ChengGumeng. Inhibitory effects of 5-lipoxygenase on oxygen-induced retinal neovascularization in mice. Chinese Journal of Ocular Fundus Diseases, 2014, 30(4): 390-394. doi: 10.3760/cma.j.issn.1005-1015.2014.04.014 Copy