PUBLICATION
Selective Inhibition of Retinal Angiogenesis by Targeting PI3 Kinase
- Authors
- Alvarez, Y., Astudillo, O., Jensen, L., Reynolds, A.L., Waghorne, N., Brazil, D.P., Cao, Y., O'Connor, J.J., and Kennedy, B.N.
- ID
- ZDB-PUB-091120-75
- Date
- 2009
- Source
- PLoS One 4(11): e7867 (Journal)
- Registered Authors
- Alvarez, Yolanda, Kennedy, Breandan N.
- Keywords
- Angiogenesis, Larvae, Zebrafish, Eyes, Vasculogenesis, Lens (anatomy), Blood vessels, Small molecules
- MeSH Terms
-
- Neovascularization, Pathologic*
- Phosphatidylinositol 3-Kinases/metabolism*
- Gene Expression Regulation, Developmental
- Retinal Vessels/pathology*
- Time Factors
- Animals
- Retina/embryology
- Retina/pathology*
- Morpholines/pharmacology
- Enzyme Inhibitors/pharmacology
- Electroretinography/methods
- Zebrafish
- Vascular Endothelial Growth Factor A/metabolism
- Hypoxia
- Chromones/pharmacology
- Inhibitory Concentration 50
- Gene Expression Regulation, Enzymologic*
- PubMed
- 19924235 Full text @ PLoS One
Citation
Alvarez, Y., Astudillo, O., Jensen, L., Reynolds, A.L., Waghorne, N., Brazil, D.P., Cao, Y., O'Connor, J.J., and Kennedy, B.N. (2009) Selective Inhibition of Retinal Angiogenesis by Targeting PI3 Kinase. PLoS One. 4(11):e7867.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping