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

Alan J Franklin; Tom L Jetton; C Lynn Kuchemann; Stephen R Russell; Elise C Kohn

doi:10.1167/iovs.03-1126

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

Journal article

Peer reviewed

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

Alan J Franklin, Tom L Jetton, C Lynn Kuchemann, Stephen R Russell and Elise C Kohn

Investigative ophthalmology & visual science, Vol.45(10), pp.3756-3766

10/2004

DOI: 10.1167/iovs.03-1126

PMID: 15452087

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Abstract

This study was performed to characterize the effects of an antimetastatic and antiangiogenic molecule, carboxyamido-triazole (CAI), on retinal neovascularization in a mouse model. 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. 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. 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.

Animals, Newborn

In Situ Nick-End Labeling

Neuroprotective Agents - therapeutic use

Retinal Vessels - metabolism

Mice, Inbred C57BL

Antineoplastic Agents - therapeutic use

Retinal Vessels - drug effects

Retinal Neovascularization - etiology

Retinal Vessels - pathology

Microscopy, Confocal

Proto-Oncogene Proteins c-bcl-2 - metabolism

Animals

Ischemia - drug therapy

Ischemia - complications

Hyperoxia - complications

Angiogenesis Inhibitors - therapeutic use

Mice

Retinal Neovascularization - drug therapy

Ischemia - pathology

Retinal Neovascularization - pathology

Disease Models, Animal

Fluorescein Angiography

Triazoles - therapeutic use

Details

Title: Subtitle: CAI is a potent inhibitor of neovascularization and imparts neuroprotection in a mouse model of ischemic retinopathy
Creators: Alan J Franklin - Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA. alfranklin@aol.com
Tom L Jetton
C Lynn Kuchemann
Stephen R Russell
Elise C Kohn
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.45(10), pp.3756-3766
DOI: 10.1167/iovs.03-1126
PMID: 15452087
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Publisher: United States
Language: English
Date published: 10/2004
Academic Unit: Ophthalmology and Visual Sciences
Record Identifier: 9983980285202771

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