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
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Copyright © the editorial department of Chinese Journal of Ocular Fundus Diseases of West China Medical Publisher. All rights reserved
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- 2. Guo Y, Wang X, Zhang X, et al. Ethanol promotes chemically inducedoral cancer in mice through activation of the 5-lipoxygenase pathway of arachidonicacid metabolism[J]. Cancer Prev Res (Phila), 2011, 4: 1863-1872.
- 3. Leedom AJ, Sullivan AB, Dong B, et al. Endogenous LXA4 circuits are determinants of pathological angiogenesis in response to chronic injury[J]. Am J Pathol, 2010, 176: 74-84.
- 4. Sapieha P, Stahl A, Chen J, et al. 5-Lipoxygenase metabolite 4-HDHA is a mediator of the antiangiogenic effect of omega-3 polyunsaturated fatty acids[J/OL]. Sci Transl Med, 2011, 3:69ra12[2011-02-09]. http://stm.sciencemag.org/content/3/69/69ra12.short..
- 5. Anand R, Kaithwas G. Anti-inflammatory potential of alpha-linolenic acid mediated through selective COX inhibition: computational and experimental data[J].Inflammation, 2014, 37:1297-1306.
- 6. Smith LE, Wesolowski E, McLellan A, et al. Oxygen-induced retinopathy in the mouse[J]. Invest Ophthalmol Vis Sci, 1994, 35:101-111.
- 7. Chatterjee M, Das S, Roy K, et al. Overexpression of 5-lipoxygenase and its relation with cell proliferation and angiogenesis in 7, 12-dimethybenz(α) anthracene-induced rat mammary carcinogenesis[J].Mol Carcinog, 2013, 52:359-369.
- 8. 黎智, 贺涛, 杜珂, 等.15-脂氧合酶-1基因转移抑制小鼠视网膜新生血管的实验研究[J].中华眼底病杂志, 2013, 29:406-410.
- 9. Cheng P, Alberts I, Li X. The role of ERK1/2 in the regulation of proliferation and differentiation of astrocytes in developing brain[J].Int J Dev Neurosci, 2013, 31:783-789.
