quantification-of-immunostained-caspase-9-in-retinal-tissue

Quantification of Immunostained Caspase-9 in Retinal Tissue

The family of caspases is known to mediate many cellular pathways beyond cell death, including cell differentiation, axonal pathfinding, and ...

in-vivo-vascular-injury-readouts-mouse-retina-to-promote

<em>In Vivo</em> Vascular Injury Readouts in Mouse Retina to Promote Reproducibility

Advancements in ophthalmic imaging tools offer an unprecedented level of access to researchers working with animal models of neurovascular injury. To ...

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.

Claire W. Chen

Department of Pathology & Cell Biology; Vagelos College of Physicians and Surgeons,
Department of Pathology & Cell Biology,
Vagelos College of Physicians and Surgeons,
Department of Pathology & Cell Biology, Vagelos College of Physicians and Surgeons

Columbia University

Quantification of Immunostained Caspase-9 in Retinal Tissue

In Vivo Vascular Injury Readouts in Mouse Retina to Promote Reproducibility