Selective inhibition of retinal angiogenesis by targeting PI3 kinase.

PloS One
Yolanda AlvarezBreandán N Kennedy

Abstract

Ocular neovascularisation is a pathological hallmark of some forms of debilitating blindness including diabetic retinopathy, age related macular degeneration and retinopathy of prematurity. Current therapies for delaying unwanted ocular angiogenesis include laser surgery or molecular inhibition of the pro-angiogenic factor VEGF. However, targeting of angiogenic pathways other than, or in combination to VEGF, may lead to more effective and safer inhibitors of intraocular angiogenesis. In a small chemical screen using zebrafish, we identify LY294002 as an effective and selective inhibitor of both developmental and ectopic hyaloid angiogenesis in the eye. LY294002, a PI3 kinase inhibitor, exerts its anti-angiogenic effect in a dose-dependent manner, without perturbing existing vessels. Significantly, LY294002 delivered by intraocular injection, significantly inhibits ocular angiogenesis without systemic side-effects and without diminishing visual function. Thus, targeting of PI3 kinase pathways has the potential to effectively and safely treat neovascularisation in eye disease.

References

Oct 28, 1994·Biochemical and Biophysical Research Communications·V Sanchez-MargáletC K Sung
Nov 23, 2000·Proceedings of the National Academy of Sciences of the United States of America·R T PetersonS L Schreiber
Apr 20, 2001·The International Journal of Biochemistry & Cell Biology·Y Cao
Aug 9, 2002·Developmental Biology·Nathan D Lawson, Brant M Weinstein
Nov 7, 2002·Cell·Derek P BrazilBrian A Hemmings
Jan 2, 2004·The New England Journal of Medicine·Robert N Frank
Feb 27, 2004·Investigative Ophthalmology & Visual Science·Peter A Campochiaro, UNKNOWN C99-PKC412-003 Study Group
Jun 11, 2004·The New England Journal of Medicine·Einar Stefánsson
Jul 9, 2004·Developmental Cell·Jesús Torres-VázquezBrant M Weinstein
Feb 3, 2005·Nature Reviews. Drug Discovery·Leonard I Zon, Randall T Peterson
Dec 16, 2005·Nature·Napoleone Ferrara, Robert S Kerbel
Feb 7, 2006·Ophthalmology·Robert L AveryMatthew J Giust
Mar 28, 2006·Nature Chemical Biology·Peter E BaylissJoanne Chan
Jul 19, 2006·Nature Reviews. Genetics·Jeffrey A EngelmanLewis C Cantley
Jan 11, 2007·Proceedings of the National Academy of Sciences of the United States of America·Michael I DorrellMartin Friedlander
Feb 17, 2007·The Biochemical Journal·Severine I GharbiMichael D Waterfield
Feb 24, 2007·American Journal of Ophthalmology·Christine Y ChenWilson J Heriot
Apr 5, 2007·Nature Protocols·Susan E Brockerhoff
Jul 3, 2007·Cell·Brendan D Manning, Lewis C Cantley
Aug 10, 2007·Expert Opinion on Investigational Drugs·Cristina Hernández, Rafael Simó
Oct 17, 2007·BMC Developmental Biology·Yolanda AlvarezBreandan N Kennedy
Mar 28, 2008·Nature·Mark E KleinmanJayakrishna Ambati
Jun 14, 2008·The New England Journal of Medicine·Rama D JagerJoan W Miller
Jul 4, 2008·Nature Reviews. Cancer·Lee M Ellis, Daniel J Hicklin
Jul 16, 2008·Advances in Cancer Research·Yihai Cao
Jan 14, 2009·Molecular Cancer Therapeutics·Nathan T Ihle, Garth Powis
Feb 10, 2009·Current Opinion in Cell Biology·Shidong JiaJean J Zhao
Apr 11, 2009·Proceedings of the National Academy of Sciences of the United States of America·Won Gil ChoJayakrishna Ambati
Apr 15, 2009·Archives of Ophthalmology·Kyoichi TakahashiPeter A Campochiaro
May 16, 2009·Mechanisms of Development·Satish S KitambiJarema J Malicki
Oct 1, 2008·Journal of Visual Impairment & Blindness·Cynthia Owsley, Gerald McGwin
Mar 24, 2010·The Journal of Cell Biology·Robert J CainAnne J Ridley
Jan 1, 2008·CSH Protocols·Valerie C FleischStephan C F Neuhauss

❮ Previous
Next ❯

Citations

Mar 19, 2013·Future Medicinal Chemistry·Alessandra GhigoEmilio Hirsch
Oct 15, 2013·Angiogenesis·Sara RezzolaMarco Presta
Feb 11, 2011·American Journal of Physiology. Cell Physiology·Huafang Wang, Yunchao Su
Jan 10, 2013·PloS One·Jun YinBreandan N Kennedy
Aug 4, 2010·Journal of Cardiovascular Translational Research·David S PealDavid Milan
Jun 5, 2012·Journal of Diabetes and Its Complications·Umesh C S YadavKota V Ramana
Sep 21, 2013·Drug Discovery Today. Technologies·Peter NovodvorskyTimothy J A Chico
Jun 15, 2011·Birth Defects Research. Part C, Embryo Today : Reviews·Lasse Dahl JensenYihai Cao
Nov 11, 2015·The Journal of Cell Biology·Hyojin ParkYoung-Guen Kwon
Dec 3, 2014·Current Opinion in Chemical Biology·Andrew J Rennekamp, Randall T Peterson
Apr 18, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Orla GalvinBreandán N Kennedy
Jun 15, 2010·Cell Communication and Signaling : CCS·Kerrie L TaylorE Elizabeth Patton
Jan 7, 2015·PLoS Biology·Andrew R DeansPaula Mabee
May 27, 2017·British Journal of Pharmacology·Stephanie L Merrigan, Breandán N Kennedy
Mar 7, 2019·Expert Opinion on Drug Discovery·Yanbin ZhaoCalum A MacRae
Nov 6, 2014·Biomolecular Concepts·Lasse Dahl JensenKeith Block
Oct 9, 2016·Journal of Tissue Engineering and Regenerative Medicine·Valeria PeruginiMatteo Santin
Feb 6, 2016·The Journal of Biological Chemistry·Alison L ReynoldsBreandán N Kennedy
Feb 26, 2020·Investigative Ophthalmology & Visual Science·Dyah W KarjosukarsoRob W J Collin
Apr 14, 2016·Experimental and Therapeutic Medicine·Xinjiang AnNan Ling
Mar 3, 2019·Developmental Biology·Rebecca WardBreandán N Kennedy
Jan 15, 2021·Developmental Biology·Naoyuki TaharaYasuhiko Kawakami
Oct 1, 2010·Developmental Biology·Carl M GayJesús Torres-Vázquez
Jan 29, 2022·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Niamh MahonBreandán Kennedy

❮ Previous
Next ❯

Methods Mentioned

BETA
sedation
confocal microscopy
light microscopy
amputation
dissecting
dissection

Software Mentioned

Photoshop
Windows Whole Cell Programme
WinWCP
OpenLab

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Cell Atlas of the Human Eye

Constructing a cell atlas of the human eye will require transcriptomic and histologic analysis over the lifespan. This understanding will aid in the study of development and disease. Find the latest research pertaining to the Cell Atlas of the Human Eye here.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Related Papers

Journal of Genetics
Yureeda QaziBalamurali K Ambati
Proceedings of the National Academy of Sciences of the United States of America
Monica GumaMichael Karin
FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
V LambertJ M Rakic
© 2022 Meta ULC. All rights reserved