Subretinal AAV2.COMP-Ang1 suppresses choroidal neovascularization and vascular endothelial growth factor in a murine model of age-related macular degeneration

Experimental Eye Research
Nathan G LambertBalamurali K Ambati

Abstract

To assess whether Tie2-mediated vascular stabilization ameliorates neovascular age-related macular degeneration (AMD), we investigated the impact of adeno-associated virus-mediated gene therapy with cartilage oligomeric matrix protein angiopoietin-1 (AAV2.COMP-Ang1) on choroidal neovascularization (CNV), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor (HIF) in a mouse model of the disease. We treated mice with subretinal injections of AAV2.COMP-Ang1 or control (AAV2.AcGFP, AAV2.LacZ, and phosphate-buffered saline). Subretinal AAV2 localization and plasmid protein expression was verified in the retinal pigment epithelium (RPE)/choroid of mice treated with all AAV2 constructs. Laser-assisted simulation of neovascular AMD was performed and followed by quantification of HIF, VEGF, and CNV in each experimental group. We found that AAV2.COMP-Ang1 was associated with a significant reduction in VEGF levels (29-33%, p < 0.01) and CNV volume (60-70%, p < 0.01), without a concomitant decrease in HIF1-α, compared to all controls. We concluded that a) AAV2 is a viable vector for delivering COMP-Ang1 to subretinal tissues, b) subretinal COMP-Ang1 holds promise as a prospective treatment for neovascular AMD, and c) alt...Continue Reading

References

Nov 1, 1984·Archives of Ophthalmology·F L FerrisL Hyman
Nov 12, 1998·The American Journal of Pathology·T TobeP A Campochiaro
Mar 31, 2000·Nature Medicine·G ThurstonG D Yancopoulos
Apr 3, 2001·Nature Reviews. Molecular Cell Biology·N JonesK Alitalo
May 27, 2003·Investigative Ophthalmology & Visual Science·Eiji SakuraiJayakrishna Ambati
Oct 25, 2003·Progress in Retinal and Eye Research·Arup Das, Paul G McGuire
Apr 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Chung-Hyun ChoGou Young Koh
Apr 14, 2004·Archives of Ophthalmology·Nathan CongdonUNKNOWN Eye Diseases Prevalence Research Group
Apr 14, 2004·Archives of Ophthalmology·David S FriedmanUNKNOWN Eye Diseases Prevalence Research Group
Apr 28, 2004·JAMA : the Journal of the American Medical Association·Neil M Bressler
Dec 31, 2004·The New England Journal of Medicine·Evangelos S GragoudasUNKNOWN VEGF Inhibition Study in Ocular Neovascularization Clinical Trial Group
Aug 30, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Fabienne BaffertDonald M McDonald
Feb 3, 2006·The Journal of Clinical Investigation·Miho NozakiJayakrishna Ambati
Apr 29, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Samuel G JacobsonWilliam W Hauswirth
Oct 20, 2007·Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift für Augenheilkunde·Peng ZhangHongjun Du
Dec 7, 2007·Investigative Ophthalmology & Visual Science·Masahiro ItayaYuichiro Ogura
Apr 29, 2008·The New England Journal of Medicine·Albert M MaguireJean Bennett
Jun 5, 2008·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Wei ZhaoGuo-Rui Dou
Jul 1, 2008·Experimental & Molecular Medicine·So Ri KimYong Chul Lee
Aug 16, 2008·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Qing XiaoShiqi Ling
Oct 16, 2008·Clinical Microbiology Reviews·Shyam Daya, Kenneth I Berns
Feb 13, 2009·American Journal of Ophthalmology·Yuko YodoiNagahisa Yoshimura
Feb 24, 2009·Nature Reviews. Molecular Cell Biology·Hellmut G AugustinKari Alitalo
Oct 21, 2009·Proceedings of the National Academy of Sciences of the United States of America·Magali Saint-GeniezPatricia A D'Amore
Dec 3, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Francesca SimonelliAlberto Auricchio
Jan 12, 2010·Biochemical and Biophysical Research Communications·Huiping GuLijun Guo
Feb 5, 2010·Investigative Ophthalmology & Visual Science·Masayuki AshikariYuichiro Ogura
Jun 23, 2010·Proceedings of the National Academy of Sciences of the United States of America·Xu HouXuri Li
Aug 18, 2010·Current Gene Therapy·Pasqualina Colella, Alberto Auricchio
Mar 30, 2011·Human Gene Therapy·Peter A Campochiaro

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Citations

Nov 4, 2016·EMBO Molecular Medicine·Jörg T RegulaGuido Hartmann
Aug 25, 2017·International Journal of Retina and Vitreous·Thiago CabralVinit B Mahajan
Aug 16, 2019·Investigative Ophthalmology & Visual Science·Keith D RochfortPhilip M Cummins
Jul 30, 2018·Vision·Praveen Yerramothu
Nov 3, 2020·Retina·Jeffrey S HeierCarlos Quezada-Ruiz

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