1. Loss of Caveolin-1 Causes Blood–Retinal Barrier Breakdown, Venous Enlargement, and Mural Cell Alteration
- Author
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Alex W. Cohen, You Yang Zhao, Xiaowu Gu, Steven J. Fliesler, William B. Stallcup, and Michael H. Elliott
- Subjects
Pathology ,medicine.medical_specialty ,Retinal Disorder ,Nitric Oxide Synthase Type III ,Retinal Artery ,Caveolin 1 ,Blood–retinal barrier ,Biology ,Permeability ,Mural cell ,Pathology and Forensic Medicine ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Blood-Retinal Barrier ,medicine ,Animals ,Humans ,030304 developmental biology ,Mice, Knockout ,0303 health sciences ,Retina ,Tight Junction Proteins ,Regular Article ,Retinal ,Retinal Vein ,Mice, Inbred C57BL ,Protein Transport ,Phenotype ,medicine.anatomical_structure ,chemistry ,Knockout mouse ,cardiovascular system ,030221 ophthalmology & optometry ,Optic nerve ,sense organs ,Biomarkers - Abstract
Blood–retinal barrier (BRB) breakdown and related vascular changes are implicated in several ocular diseases. The molecules and mechanisms regulating BRB integrity and pathophysiology are not fully elucidated. Caveolin-1 (Cav-1) ablation results in loss of caveolae and microvascular pathologies, but the role of Cav-1 in the retina is largely unknown. We examined BRB integrity and vasculature in Cav-1 knockout mice and found a significant increase in BRB permeability, compared with wild-type controls, with branch veins being frequent sites of breakdown. Vascular hyperpermeability occurred without apparent alteration in junctional proteins. Such hyperpermeability was not rescued by inhibiting eNOS activity. Veins of Cav-1 knockout retinas exhibited additional pathological features, including i) eNOS-independent enlargement, ii) altered expression of mural cell markers (eg, down-regulation of NG2 and up-regulation of αSMA), and iii) dramatic alterations in mural cell phenotype near the optic nerve head. We observed a significant NO–dependent increase in retinal artery diameter in Cav-1 knockout mice, suggesting that Cav-1 plays a role in autoregulation of resistance vessels in the retina. These findings implicate Cav-1 in maintaining BRB integrity in retinal vasculature and suggest a previously undefined role in the retinal venous system and associated mural cells. Our results are relevant to clinically significant retinal disorders with vascular pathologies, including diabetic retinopathy, uveoretinitis, and primary open-angle glaucoma.
- Published
- 2014
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