Effects of the phosphatidylinositol 3-kinase inhibitor in a mouse model of retinal neovascularization.
OBJECTIVE
To determine the effects of LY294002, a phosphatidylinositol 3-kinase inhibitor, on suppressing experimental retinal neovascularization in an animal model of ischemic retinopathy.


METHODS
The effect of LY294002 on the survival of RF/6A cells stimulated by vascular endothelial growth factor (VEGF) was investigated colorimetrically. The inhibitory activity of LY294002 on the migration of cells stimulated with VEGF was measured by cell counting. C57BL/6N mice at postnatal day (P) 7 were exposed to 75 +/- 2% oxygen for 5 days (P7-P11) and then returned to room air for 5 days (P12-P17) to induce retinal neovascularization. Beginning on P12, mice received daily intraperitoneal injections of LY294002 or dimethyl sulfoxide and phosphate-buffered saline (control) through P17. Retinal neovascularization was examined by adenosine diphosphatase staining after 5 days in room air and was quantitated histologically by counting the neovascular endothelial cell nuclei anterior to the inner limiting membrane.


RESULTS
LY294002 significantly inhibited VEGF-induced survival and migration. LY294002-treated and control animals demonstrated no perfusion regions in the posterior retina. Retinas from control mice at P17 contained neovascular tufts at the junction between the perfused and nonperfused retina. The tufts contained numerous neovascular nuclei. Retinas from mice treated with LY294002 demonstrated a significant reduction in neovascular cell nuclei compared with control mice.


CONCLUSIONS
LY294002 significantly inhibits retinal neovascularization in a mouse model of retinal neovascularization.
Yu
Wen-Zhen
WZ
Department of Ophthalmology, Peking University People's Hospital, Beijing, PR China.
Zou
He
H
Li
Xiao-Xin
XX
Yan
Zheng
Z
Dong
Jian-Qiang
JQ
D000818:Animals; D000831:Animals, Newborn; D001081:Apyrase / Q000032:analysis; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007511:Ischemia / Q000150:complications; D008253:Macaca mulatta; D051379:Mice; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000494:pharmacology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012160:Retina / Q000187:drug effects / Q000201:enzymology; D015861:Retinal Neovascularization / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D012171:Retinal Vessels; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D001081:Apyrase