CAI is a potent inhibitor of neovascularization and imparts neuroprotection in a mouse model of ischemic retinopathy

被引:5
作者
Franklin, AJ
Jetton, TL
Kuchemann, CL
Russell, SR
Kohn, EC
机构
[1] Univ Iowa Hosp & Clin, Dept Ophthalmol, Iowa City, IA 52242 USA
[2] Univ Iowa Hosp & Clin, Dept Anim Care, Iowa City, IA 52242 USA
[3] Univ Vermont, Dept Endocrinol, Burlington, VT USA
[4] NCI, Pathol Lab, Mol Signaling Sect, Bethesda, MD 20892 USA
关键词
D O I
10.1167/iovs.03-1126
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
PURPOSE. This study was performed to characterize the effects of an antimetastatic and antiangiogenic molecule, carboxyamidotriazole (CAI), on retinal neovascularization in a mouse model. METHODS. Neonatal mice were subjected to 75% to 85% oxygen from postnatal day (PND)-7 to -12 and then were abruptly placed in room air. CAI ( 100 mg/kg) or vehicle control polyethylene glycol-400 (PEG-400) was given daily from PND-14 to - 16, and mice were killed on PND-17 to form group A. In group B, CAI ( 100 mg/kg) or PEG-400 was given daily from PND-17 to - 19, and mice were killed on PND-20. RESULTS. A 92% inhibition of neovascular cell nuclei on light microscopy was observed in mice treated with CAI in group A ( P < 0.0001). Fluorescein-perfusion demonstrated a similar profound inhibition of neovascular frond formation in CAI-treated mice in group A. In group B, after neovascular fronds had already formed, CAI administration reduced neovascular cell nuclei by 72% ( P < 0.001). Fluorescein perfusion studies confirmed that CAI induced regression of neovascular fronds. Similar amounts of posterior retinal ischemia were observed in all mice at both PND-17 and - 20. In group A and B animals, CAI increased immunoreactivity of a cellular survival factor, Bcl-2, decreased TUNEL-positive cells, and after CAI treatment the normal morphology of the inner retina remained intact. CONCLUSIONS. CAI almost completely abolished retinal neovascularization in group A, and neovascular fronds involuted after treatment with CAI in group B. Thus, CAI is a potent inhibitor of ischemia-induced neovascularization and also imparts retinal neuroprotection after ischemic injury.
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收藏
页码:3756 / 3766
页数:11
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