optimization-retinal-vein-occlusion-mouse-model-to-limit

Optimization of the Retinal Vein Occlusion Mouse Model to Limit Variability

Mouse models of retinal vein occlusion (RVO) are often used in ophthalmology to study hypoxic-ischemic injury in the neural retina. In this report, a ...

Columbia University

Columbia College

Central nervous system ischemic injury features neuronal dysfunction, inflammation and breakdown of vascular integrity. Here we show that activation of endothelial caspase-9 after hypoxia-ischemia is a critical event in subsequent dysfunction of the blood-retina barrier, using a panel of interrelated ophthalmic in vivo imaging measures in a mouse model of retinal vein occlusion (RVO). Rapid nonapoptotic activation of caspase-9 and its downstream effector caspase-7 in endothelial cells promotes capillary ischemia and retinal neurodegeneration. Topical eye-drop delivery of a highly selective caspase-9 inhibitor provides morphological and functional retinal protection. Inducible endothelial-specific caspase-9 deletion phenocopies this protection, with attenuated retinal edema, reduced inflammation and preserved neuroretinal morphology and function following RVO. These results reveal a non-apoptotic function of endothelial caspase-9 which regulates blood-retina barrier integrity and neuronal survival, and identify caspase-9 as a therapeutic target in neurovascular disease.

Endothelial activation of caspase-9 promotes neurovascular injury in retinal vein occlusion.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Anna Potenski

Department of Molecular Pharmacology and Therapeutics; Vagelos College of Physicians and Surgeons

Columbia University

Optimization of the Retinal Vein Occlusion Mouse Model to Limit Variability

Anna Potenski

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Molecular Pharmacology and Therapeutics; Vagelos College of Physicians and Surgeons

Columbia University

Optimization of the Retinal Vein Occlusion Mouse Model to Limit Variability

Department of Molecular Pharmacology and Therapeutics; Vagelos College of Physicians and Surgeons