@article {742276,
	title = {Blockage of PI3K/mTOR Pathways Inhibits Laser-Induced Choroidal Neovascularization and Improves Outcomes Relative to VEGF-A Suppression Alone.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {57},
	number = {7},
	year = {2016},
	month = {2016 Jun 1},
	pages = {3138-44},
	abstract = {PURPOSE: Choroidal neovascularization (CNV) is a major cause of visual loss with age-related macular degeneration (AMD). We evaluated whether blockade of phosphatidyl-inositol-3-kinase (PI3K) and the mammalian target of rapamycin (mTOR), by impairing VEGF-A and other growth factor receptors like platelet-derived growth factor (PDGF), would reduce laser-induced CNV in mice. METHODS: Choroidal neovascularization lesions were induced in C57BL/6 mice. Two groups of mice received oral GSK2126458 (3 mg/kg) or vehicle for 14 days following laser, whereas three groups were treated with GSK2126458 (6 μg/eye), aflibercept (2 μL/eye), or vehicle intravitreally on days 0 and 7 after laser. Vascular leakage was measured by fluorescein angiography (FA) on day 14. Choroidal neovascularization membranes were evaluated on choroidal flat mounts following FITC-dextran perfusion, as well as ED1 and isolectin B4 (IB4) immunohistochemistry. RESULTS: Oral and intravitreal (IVT) GSK2126458 reduced leakage and area of CNV lesions. Greater probability of leaking lesions (\~{}60\%; P \&lt; 0.05) was observed in both vehicle groups. Fluorescein isothiocyanate-dextran-labeled total CNV burden area (total lesion area/eye) was reduced \~{}67\% (P \&lt; 0.05) and 35\% (P = 0.0528) after oral and IVT GSK2126458 administration. GSK2126458 treatment reduced lesion size by \~{}80\% (P \&lt; 0.05) and 50\% (P \&lt; 0.05) for oral and IVT control groups. Aflibercept did not alter lesion size (\~{}27\% reduction). CONCLUSIONS: Phosphatidyl-inositol-3-kinase/mTOR is involved in laser-induced CNV angiogenic processes. GSK2126458 effectively reduces CNV size and leakage. Choroidal neovascularization size following IVT GSK2126458 was smaller than after oral administration. Therefore, inhibition of PI3K/mTOR pathways may be more effective due to blockade of action of multiple growth factors.},
	issn = {1552-5783},
	doi = {10.1167/iovs.15-18795},
	author = {Ma, Jie and Sun, Yu and L{\'o}pez, Francisco J and Adamson, Peter and Kurali, Edit and Lashkari, Kameran}
}
