miR-191 inhibits oxygen-induced retinal neovascularization in mice_Chinese Journal of Ocular Fundus Diseases

Authors：

Liu Boshi , Dong Lijie , Li Xiaorong , Zhang Yan , Zhang Mingliang , Liu Xun , Huang Liangyu , Wu Mianmian , Xu Manhong , Su Ruihong , Zhang zhe ,  Han Jindong

Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, Tianjin Medical University School of Optometry and Ophthalmology, Tianjin 300384, ChinaLiu Boshi and Dong Lijie are contributed equally to the article;

Corresponding author：

Han Jindong, Email: djindonghan@126.com

Keywords：

Retinal neovascularization/prevention &control; Lentivirus infections; Animal experimentation

DOI：

10.3760/cma.j.issn.1005-1015.2019.05.010

Video：

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Objective To observe the inhibitory effect of lentiviral vector miR-191 (LV-191) on retinal neovascularization (RNV) in mice model of oxygen-induced retinopathy (OIR).Methods Eighty healthy 7-day-old C57BL/6J mice were randomly divided into 5 groups including normal group, non-intervention group, normal saline (NS) group, LV-191 group and LV-green fluorescent protein (GFP) group, 16 mice in each group. The OIR model was established in the non-intervention group, NS group, LV-191 group and LV-GFP group. NS group, LV-191 group and LV-GFP group were given an intravitreal injection of 1 μl of NS, LV-191 and LV-GFP at the age of 12 days. No injection was performed in the non-intervention group. In normal group,newborn mouse were maintained in room air form P0 to P17, and no treatment was performed. Mice in all five groups were euthanized at P17. Retinal neovasculation (RNV) was evaluated by counting the number of pre-retinal neovascular cells and analysis of non-perfusion area area by immunofluorescent staining of the mouse retina. Real-time quantitative PCR (RT-PCR) to detect miR -191 and P21 expression of retinal tissue.Results In the LV-191 group, the non-perfusion area were both significantly smaller than those in non-intervention group, NS group and LV-GFP group (F=127.20, P＜0.001). The number of pre-retinal neovascular cell nuclei in retinas from LV-191 group were obviously lower than those in the retinas from non-intervention group, NS group and LV-GFP group (F=31.71, P＜0.05). RT-PCR showed that the LV-191 and P21 level of LV-191 group increased significantly than other groups (F=10.95, 15.60; P＜0.05).Conclusion Intravitreal injection of LV-191 inhibits RNV in mice model of OIR possibly through up-regulating p21.

Citation： Liu Boshi, Dong Lijie, Li Xiaorong, Zhang Yan, Zhang Mingliang, Liu Xun, Huang Liangyu, Wu Mianmian, Xu Manhong, Su Ruihong, Zhang zhe, Han Jindong. miR-191 inhibits oxygen-induced retinal neovascularization in mice. Chinese Journal of Ocular Fundus Diseases, 2019, 35(5): 475-479. doi: 10.3760/cma.j.issn.1005-1015.2019.05.010 Copy

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1. 张哲,刘巨平,刘竹青,等. 高糖状态下视网膜血管内皮细胞基因表达谱的RNA-Seq分析[J].中华眼底病杂志, 2018, 34(4): 377-381. DOI: 10.3760/cma.j.issn.1005-1015.2018.04.014.Zhang Z,Liu JP,Liu ZQ,et al. RNA-Seq analysis of gene expression profiling in retinal vascular endothelial cells under high glucose condition[J]. Chin J Ocul Fundus Dis, 2018, 34(4): 377-381. DOI: 10.3760/cma.j.issn.1005-1015.2018.04.014.
2. 牛瑞,马腾,杜雪利,等.抗血管内皮生长因子药物治疗后视网膜血管内皮细胞基因表达谱的RNA-Seq分析[J]. 中华眼底病杂志, 2018, 34(3): 275-280. DOI: 10.3760/cma.j.issn.1005-1015.2018.03.016.Niu R,Ma T,Du XL,et al. RNA-Seq analysis of gene expression profiling in human retinal vascular endothelial cells after anti-vascular endothecial growth factor treatment[J]. Chin J Ocul Fundus Dis, 2018, 34(3): 275-280. DOI: 10.3760/cma.j.issn.1005-1015.2018.03.016.
3. Trzybulska D, Vergadi E, Tsatsanis C. miRNA and other non-coding RNA as promising diagnostic markers[J]. EJIFCC, 2018, 29(3): 221-226.
4. Chen N, Wang J, Hu Y, et al.MicroRNA-410 reduces the expression of vascular endothelial growth factor and inhibits oxygen-induced retinal neovascularization[J/OL].PLoS One, 2014, 9(4): 95665[2014-04-28].https://doi.org/10.1371/journal.pone.0095665. DOI:10.1371/journal.pone.0095665.
5. Shen J, Yang X, Xie B, et al. MicroRNAs regulate ocular neovascularization[J]. Mol Ther, 2008, 16(7): 1208-1216. DOI: 10.1038/mt.2008.104.
6. Han S, Kong YC, Sun B, et al. microRNA-218 inhibits oxygen-induced retinal neovascularization via reducing the expression of roundabout 1[J]. Chin Med J (Engl), 2016, 129(6): 709-715. DOI: 10.4103/0366-6999.178013.
7. Nagpal N, Kulshreshtha R. miR-191: an emerging player in disease biology[J]. Front Genet, 2014, 5: 99. DOI: 10.3389/fgene.2014.00099.
8. Gu Y, Ampofo E, Menger MD, et al. miR-191 suppresses angiogenesis by activation of NF-κB signaling[J]. FASEB J, 2017, 31(8): 3321-3333. DOI: 10.1096/fj.201601263R.
9. Smith LEH, Wesoloiuski E, Mclellan A, et al. Oxygen-induced retinopath in the mouse[J]. Invest Ophthalmol Vis Sci, 1994, 35: 101-111.
10. 谷中秀, 姜静, 黄敏, 等. 不同批次的重组诱饵型受体创新药物RC28-E1与RC28-E2对视网膜新生血管的药效学比较及机制[J]. 中华实验眼科杂志, 2018, 36(8): 581-589. DOI: 10.3760/cma.j.issn.2095-0160.2018.08.002.Gu ZX, Jiang J, Huang M, et al. Comparison of pharmacodynamics between different batches of recombinant decoy receptor innovative drug RC28-E1 and RC28-E2 in retinal angiogenesis and neovascularization and its mechanism[J]. Chin J Exp Ophthalmol, 2018, 36(8): 581-589. DOI: 10.3760/cma.j.issn.2095-0160.2018.08.002.
11. He H, Liu R, Xiong W, et al. Lentiviral vector-mediated down-regulation of Notch1 in endometrial stem cells results in proliferation and migration in endometriosis[J]. Mol Cell Endocrinol, 2016, 434: 210-218. DOI: 10.1016/j.mce.2016.07.004.
12. Min X, Zhou Q, Dong X, et al. Expression profile and regulation of telomerase reverse transcriptase on oxygen-induced retinal neovascularization[J]. Curr Eye Res, 2011, 36(2): 135-142. DOI: 10.3109/02713683.2010.525679.
13. Liu CH, Sun Y, Li J, et al. Endothelial microRNA-150 is an intrinsic suppressor of pathologic ocular neovascularization[J]. Proc Natl Acad Sci USA, 2015, 112(39): 12163-12168. DOI: 10.1073/pnas.1508426112.
14. Wang P, Luo Y, Duan H, et al. MicroRNA 329 suppresses angiogenesis by targeting CD146[J]. Mol Cell Biol, 2013, 33(18): 3689-3699. DOI: 10.1128/MCB.00343-13.
15. Colamaio M, Borbone E, Russo L, et al. miR-191 down-regulation plays a role in thyroid follicular tumors through CDK6 targeting[J]. J Clin Endocrinol Metab, 2011, 96(12): 1915-1924. DOI: 10.1210/jc.2011-0408.
16. Kim JH, Lee BJ, Kim JH, et al. Rosmarinic acid suppresses retinal neovascularization via cell cycle arrest with increase of p21(WAF1) expression[J]. Eur J Pharmacol, 2009, 615(1-3): 150-154. DOI: 10.1016/j.ejphar.2009.05.015.
17. Han J, Li N. Adenoviral vector-mediated delivery of p21WAF1/CIP1 prevents retinal neovascularization in an oxygen-induced retinopathy model[J]. Curr Eye Res, 2016, 41(8): 1113-1117. DOI: 10.3109/02713683.2015.1090002.

Chinese Journal of Ocular Fundus Diseases

miR-191 inhibits oxygen-induced retinal neovascularization in mice

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