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Abstract #11506 Published in IGR 6-3
CAI is a potent inhibitor of neovascularization and imparts neuroprotection in a mouse model of ischemic retinopathy
Franklin AJ; Jetton TL; Kuchemann CL; Russell SR; Kohn ECInvestigative Ophthalmology and Visual Science 2004; 45: 3756-3766
PURPOSE: This study was performed to characterize the effects of an antimetastatic and antiangiogenic molecule, carboxyamido-triazole (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.
Dr. A.J. Franklin, Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA. alfranklin@aol.com
Classification:
11.5 Carbonic anhydrase inhibitors (Part of: 11 Medical treatment)