Intravitreal AAV2.COMP-Ang1 Prevents Neurovascular Degeneration in a Murine Model of Diabetic Retinopathy

Diabetes
Judd M CahoonBalamurali K Ambati

Abstract

Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population in the U.S. The vision-threatening processes of neuroglial and vascular dysfunction in DR occur in concert, driven by hyperglycemia and propelled by a pathway of inflammation, ischemia, vasodegeneration, and breakdown of the blood retinal barrier. Currently, no therapies exist for normalizing the vasculature in DR. Here, we show that a single intravitreal dose of adeno-associated virus serotype 2 encoding a more stable, soluble, and potent form of angiopoietin 1 (AAV2.COMP-Ang1) can ameliorate the structural and functional hallmarks of DR in Ins2Akita mice, with sustained effects observed through six months. In early DR, AAV2.COMP-Ang1 restored leukocyte-endothelial interaction, retinal oxygenation, vascular density, vascular marker expression, vessel permeability, retinal thickness, inner retinal cellularity, and retinal neurophysiological response to levels comparable with nondiabetic controls. In late DR, AAV2.COMP-Ang1 enhanced the therapeutic benefit of intravitreally delivered endothelial colony-forming cells by promoting their integration into the vasculature and thereby stemming further visual decline. AAV2.COMP-Ang1 single-dose ge...Continue Reading

References

Jun 15, 1996·The Journal of Clinical Investigation·M MizutaniM Lorenzi
Mar 31, 2000·Nature Medicine·G ThurstonG D Yancopoulos
Jan 6, 2001·The American Journal of Pathology·A M JoussenA P Adamis
May 10, 2002·The American Journal of Pathology·Antonia M JoussenAnthony P Adamis
Sep 1, 1961·Archives of Ophthalmology·D G COGANT KUWABARA
Jan 2, 2004·The New England Journal of Medicine·Robert N Frank
Apr 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Chung-Hyun ChoGou Young Koh
Jul 3, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Antonia M JoussenAnthony P Adamis
Mar 19, 2005·The British Journal of Ophthalmology·J I PatelI A Cree
May 26, 2005·Investigative Ophthalmology & Visual Science·Alistair J BarberSarah K Bronson
Jun 27, 2006·Investigative Ophthalmology & Visual Science·Matthew J GastingerAlistair J Barber
Nov 17, 2006·Journal of Neuroimmunology·Stanley A VinoresPeter A Campochiaro
Jan 29, 2008·Current Diabetes Reviews·Rakesh ChibberEva M Kohner
Jun 3, 2008·Investigative Ophthalmology & Visual Science·Matthew J GastingerAlistair J Barber
Jan 20, 2009·Investigative Ophthalmology & Visual Science·Hille W van DijkMichael D Abràmoff
Feb 24, 2009·Nature Reviews. Molecular Cell Biology·Hellmut G AugustinKari Alitalo
Oct 9, 2009·Kidney International·Duk Hoon KimWon Kim
Nov 4, 2009·Journal of Neuroscience Research·Hye Young ShinSun Ha Paek
Dec 3, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Francesca SimonelliAlberto Auricchio
Apr 30, 2010·Ophthalmology·UNKNOWN Diabetic Retinopathy Clinical Research NetworkJennifer K Sun
Jun 18, 2010·Investigative Ophthalmology & Visual Science·Reinhold J MedinaAlan W Stitt
Feb 12, 2011·Investigative Ophthalmology & Visual Science·Lu YinWilliam H Merigan
Jul 21, 2011·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Fanxia ShenHua Su
Feb 4, 2012·Diabetes Care·Joanne W Y YauUNKNOWN Meta-Analysis for Eye Disease (META-EYE) Study Group
Dec 12, 2012·Investigative Ophthalmology & Visual Science·Zongchao HanMuna I Naash
Feb 2, 2013·Investigative Ophthalmology & Visual Science·Moe H AungMachelle T Pardue
Apr 11, 2013·Investigative Ophthalmology & Visual Science·Sergio CaballeroMaria B Grant
Dec 18, 2013·Experimental Eye Research·Judd M CahoonBalamurali K Ambati
Oct 14, 2014·Molecular Therapy : the Journal of the American Society of Gene Therapy·Xiaohui ZhangBalamurali K Ambati
May 2, 2015·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·S O SyrjäläK B Lemström

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Citations

Feb 26, 2016·Current Opinion in Endocrinology, Diabetes, and Obesity·Thomas W Gardner, Emily Y Chew
Jun 18, 2016·Stem Cells International·Cai-Guo YuDong Zhao
Jan 4, 2017·Journal of Diabetes·Yi Shi, Paul M Vanhoutte
May 23, 2017·Nature Reviews. Drug Discovery·Pipsa SaharinenKari Alitalo
Nov 4, 2016·EMBO Molecular Medicine·Jörg T RegulaGuido Hartmann
Jul 25, 2019·Chinese Medical Journal·Ling-Bing MengTao Gong
Oct 5, 2017·Biomolecules·Pratiek N MatkarKrishna K Singh
Aug 15, 2020·BMJ Open Diabetes Research & Care·Mi TianYufeng Huang
Feb 16, 2017·Drugs·Sanket U Shah, Raj K Maturi
Jun 12, 2019·Investigative Ophthalmology & Visual Science·Lara S CarrollBalamurali K Ambati
Oct 15, 2019·Current Eye Research·Pietro Maria BertelliReinhold J Medina
Sep 6, 2019·Journal of Diabetes Research·Michael WhiteheadKeith R Martin
Aug 16, 2019·Investigative Ophthalmology & Visual Science·Keith D RochfortPhilip M Cummins
Nov 22, 2018·Frontiers in Medicine·Christina L O'NeillReinhold J Medina
Oct 11, 2020·International Journal of Molecular Sciences·Pawan FarisFrancesco Moccia
Nov 3, 2020·Retina·Jeffrey S HeierCarlos Quezada-Ruiz
Jan 21, 2021·Nature Reviews. Endocrinology·David A AntonettiAlan W Stitt
Dec 12, 2020·Cells·Shin-Ichiro HayashiRyuichi Morishita
May 7, 2021·International Ophthalmology·Deepak SoniBrijesh Takkar

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Methods Mentioned

BETA
dissection
confocal microscopy
light microscopy
Assay
Fluorescence
density gradient fractionation
transfection

Software Mentioned

OCT
ImageJ
Excel

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