assessing-leukocyte-endothelial-interactions-under-flow-conditions-an

Assessing Leukocyte-endothelial Interactions Under Flow Conditions in an <em>Ex Vivo</em> Autoperfused Microflow Chamber Assay

Leukocyte-endothelial interactions are early and critical events in acute and chronic inflammation and can, when dysregulated, mediate tissue injury ...

Harvard Medical School, Massachusetts Eye & Ear Infirmary

St. Elizabeth's Medical Center

Regulatory T cells in blood of patients with birdshot retinochoroidopathy.

Ocular neovascularization, including age-related macular degeneration (AMD), is a primary cause of blindness in individuals of industrialized countries. With a projected increase in the prevalence of these blinding neovascular diseases, there is an urgent need for new pharmacological interventions for their treatment or prevention. Increasing evidence has implicated eicosanoid-like metabolites of long-chain polyunsaturated fatty acids (LCPUFAs) in the regulation of neovascular disease. In particular, metabolites generated by the cytochrome P450 (CYP)-epoxygenase pathway have been shown to be potent modulators of angiogenesis, making this pathway a reasonable previously unidentified target for intervention in neovascular ocular disease. Here we show that dietary supplementation with ω-3 LCPUFAs promotes regression of choroidal neovessels in a well-characterized mouse model of neovascular AMD. Leukocyte recruitment and adhesion molecule expression in choroidal neovascular lesions were down-regulated in mice fed ω-3 LCPUFAs. The serum of these mice showed increased levels of anti-inflammatory eicosanoids derived from eicosapentaenoic acid and docosahexaenoic acid. 17,18-epoxyeicosatetraenoic acid and 19,20-epoxydocosapentaenoic acid, the major CYP-generated metabolites of these primary ω-3 LCPUFAs, were identified as key lipid mediators of disease resolution. We conclude that CYP-derived bioactive lipid metabolites from ω-3 LCPUFAs are potent inhibitors of intraocular neovascular disease and show promising therapeutic potential for resolution of neovascular AMD.

Article	Year
Regulatory T cells in blood of patients with birdshot retinochoroidopathy. Ophthalmology\| PubMed ID: 23374570	2013
Cytochrome P450-generated metabolites derived from ω-3 fatty acids attenuate neovascularization. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 24979774	2014

Lama Mulki

Biography

JoVE Journal Publications

Other Publications