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FASEB J. 2017 Mar;31(3):1107-1119. doi: 10.1096/fj.201600351R. Epub 2016 Dec 14.

Lebecetin, a C-type lectin, inhibits choroidal and retinal neovascularization.

Author information

1
Sorbonne Universités, Université Pierre et Marie Curie, INSERM, Centre National de la Recherche Scientifique, Institut de la Vision, Paris, France.
2
Laboratoire des Venins et Biomolécules Thérapeutiques LR11IPT08, Institut Pasteur de Tunis, Tunis, Tunisia.
3
Université de Carthage, Faculté des Sciences de Bizerte, Bizerte, Tunisia.
4
Sorbonne Universités, Université Pierre et Marie Curie, INSERM, Centre National de la Recherche Scientifique, Institut de la Vision, Paris, France; xavier.guillonneau@inserm.fr.

Abstract

Angiogenesis is a cause of visual impairment and blindness in the wet form of age-related macular degeneration and in ischemic retinopathies. Current therapies include use of anti-VEGF agents to reduce choroidal neovascularization (CNV) and edema. These treatments are effective in most cases, but spontaneous or acquired resistance to anti-VEGF and possible adverse effects of long-term VEGF inhibition in the retina and choroid highlight a need for additional alternative therapies. Integrins αvβ3 and αvβ5, which regulate endothelial cell proliferation and stabilization, have been implicated in ocular angiogenesis. Lebecetin (LCT) is a 30-kDa heterodimeric C-type lectin that is isolated from Macrovipera lebetina venom and interacts with α5β1- and αv-containing integrins. We previously showed that LCT inhibits human brain microvascular endothelial cell adhesion, migration, proliferation, and tubulogenesis. To evaluate the inhibitory effect of LCT on ocular angiogenesis, we cultured aortic and choroidal explants in the presence of LCT and analyzed the effect of LCT on CNV in the mouse CNV model and on retinal neovascularization in the oxygen-induced retinopathy model. Our data demonstrate that a single injection of LCT efficiently reduced CNV and retinal neovascularization in these models.-Montassar, F., Darche, M., Blaizot, A., Augustin, S., Conart, J.-B., Millet, A., Elayeb, M., Sahel, J.-A., Réaux-Le Goazigo, A., Sennlaub, F., Marrakchi, N., Messadi, E., Guillonneau, X. Lebecetin, a C-type lectin, inhibits choroidal and retinal neovascularization.

KEYWORDS:

angiogenesis; integrins; macular degeneration; retinopathy; snake venom

PMID:
27974593
DOI:
10.1096/fj.201600351R
[Indexed for MEDLINE]

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