HIF-1&alpha; siRNA reduces retinal neovascularization in a mouse model of retinopathy of prematurity

XU Hui-Zhuo; LIU Shuang-Zhen; XIONG Si-Qi; XIA Xiao-Bo

PDF(1095 KB)

Chinese Journal of Contemporary Pediatrics ›› 2011, Vol. 13 ›› Issue (8) : 680-683.

EXPERIMENTAL RESEARCH

HIF-1α siRNA reduces retinal neovascularization in a mouse model of retinopathy of prematurity

XU Hui-Zhuo, LIU Shuang-Zhen, XIONG Si-Qi, XIA Xiao-Bo

Author information +

History +

Abstract

OBJECTIVE: To study the inhibition effect of HIF-1α specific siRNA expression vector pSUPERH1-siHIF-1α on retinal neovascularization in a mouse model of retinopathy of prematurity (ROP). METHODS: The mouse model of ROP was prepared by the method Smith described. Forty-eight ROP mice were randomly divided into two groups: an experimental group that was intravitreously injected with pSUPERH1-siHIF-1α and a control group that was injected with pSUPER retro vector. The levels of HIF-1α and vascular endothelia growth factor (VEGF) in the retina were examined by Western blot. The retinal neovascularization was evaluated by angiography using FITC Dextran and quantitated histologically. RESULTS: The levels of HIF-1α and VEGF in the retina in the experimental group were reduced 90% and 65% respectively compared with those in the control group. Meanwhile, the number of retinal neovascular endothelial nucleus outbreaking the inner limit membrane in the experimental group was significantly reduced compared with that in the control group. CONCLUSIONS: The development of retinal neovascularization of ROP can be markedly inhibited by RNA interference targeting HIF-1α.

Key words

Hypoxia inducible factor-1α / RNA interference / Retinopathy of prematurity / Retinal neovascularization / Mice

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

XU Hui-Zhuo, LIU Shuang-Zhen, XIONG Si-Qi, XIA Xiao-Bo. HIF-1α siRNA reduces retinal neovascularization in a mouse model of retinopathy of prematurity[J]. Chinese Journal of Contemporary Pediatrics. 2011, 13(8): 680-683

References

［1］The Committee for the Classification of Retinopathy of Prematurity. An international classification of retinopathy of prematurity［J］. Arch Ophthalmol, 1984,102(8): 1130-1134.

［2］李秋平, 王宗华, 陈耀琴, 陈佳, 黄捷婷, 王自珍，等. 床旁激光治疗早产儿视网膜病变的疗效分析［J］. 中国当代儿科杂志， 2010,12(9): 693-695.

［3］Simó R, Carrasco E, García-Ramírez M, Hernández C. Angiogenic and antiangiogenic factors in proliferative diabetic retinopathy［J］. Curr Diabetes Rev, 2006, 2(1):71-98.

［4］Robinson GS, Pierce EA, Rook SL, Foley E, Webb R, Smith LE. Oligodeoxynucleotides inhibit retinal neovascularization in a murine model of proliferative retinopathy［J］. Proc Natl Acad Sci U S A, 1996, 93(10): 4851-4856.

［5］Bainbridge JW, Mistry A, De Alwis M, Paleolog E, Baker A, Thrasher AJ, et al. Inhibition of retinal neovascularisation by gene transfer of soluble VEGF receptor sFlt1［J］. Gene Ther, 2002, 9(5): 320-326.

［6］Rosmorduc O, Housset C. Hypoxia: a link between fibrogenesis, angiogenesis, and carcinogenesis in liver disease［J］. Semin Liver Dis, 2010, 30(3): 258-270.

［7］Westra J, Molema G, Kallenberg CG. Hypoxia-inducible factor-1 as regulator of angiogenesis in rheumatoid arthritis-therapeutic implications［J］. Curr Med Chem, 2010, 17(3): 254-263.

［8］许惠卓，刘双珍，夏晓波，熊思齐，王育科，李岩，等，低氧诱导因子1α干扰RNA对血管内皮生长因子mRNA表达的抑制作用［J］. 眼视光学杂志，2007，9(4)：228-231.

［9］熊宇，夏晓波，许惠卓，蒋剑，宋伟涛，刘双珍，等，干扰RNA 抑制小鼠视网膜HIF1α蛋白质的表达［J］. 国际眼科杂志， 2007,7(2):361-364.

［10］Smith LE, Wesolowski E, McLellan A, Kostyk SK, D’Amato R, Sullivan R, et al. Oxygen-induced retinopathy in the mouse［J］. Invest Ophthalmol Vis Sci, 1994, 35(1): 101-111.

［11］Ozaki H, Yu AY, Della N, Ozaki K, Luna JD, Yamada H, et al. Hypoxia inducible factor-1alpha is increased in ischemic retina: temporal and spatial correlation with VEGF expression［J］. Invest Ophthalmol Vis Sci, 1999, 40(1): 182-189.

［12］Masuda I, Matsuo T, Yasuda T, Matsuo N. Gene transfer with the intraocular tissues by different routes of administration［J］. Invest Ophthalmol Vis Sci, 1996, 345（37）: 1914-1920.

［13］Lipardi C, Wei Q, Paterson BM. RNAi as random degradative PCR: siRNA primers convert mRNA into dsRNAs that are degraded to generate new siRNAs［J］. Cell, 2001, 107(3): 297-307.

［14］Takahashi R, Tanaka S, Hiyama T, Ito M, Kitadai Y, Sumii M, et al. Hypoxia-inducible factor-1alpha expression and angiogenesis in gastrointestinal stromal tumor of the stomach［J］. Oncol Rep, 2003, 10(4): 797-802.

［15］Frank RN. Diabetic retinopathy［J］. N Engl J Med, 2004, 350(1):48-58.