Montassar Fadoua, Darche Marie, Blaizot Amandine, Augustin Sébastien, Conart Jean-Baptiste, Millet Aurélie, Elayeb Mohamed, Sahel José-Alain, Réaux-Le Goazigo Annabelle, Sennlaub Florian, Marrakchi Naziha, Messadi Erij, Guillonneau Xavier
Sorbonne Universités, Université Pierre et Marie Curie, INSERM, Centre National de la Recherche Scientifique, Institut de la Vision, Paris, France.
Laboratoire des Venins et Biomolécules Thérapeutiques LR11IPT08, Institut Pasteur de Tunis, Tunis, Tunisia.
FASEB J. 2017 Mar;31(3):1107-1119. doi: 10.1096/fj.201600351R. Epub 2016 Dec 14.
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 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.
血管生成是湿性年龄相关性黄斑变性和缺血性视网膜病变导致视力损害和失明的一个原因。目前的治疗方法包括使用抗血管内皮生长因子（VEGF）药物来减少脉络膜新生血管（CNV）和水肿。这些治疗在大多数情况下是有效的，但对VEGF的自发或获得性耐药以及视网膜和脉络膜长期VEGF抑制可能产生的不良反应凸显了对其他替代疗法的需求。整合素αvβ3和αvβ5可调节内皮细胞增殖和稳定性，与眼部血管生成有关。勒贝菌素（LCT）是一种30 kDa的异二聚体C型凝集素，从毒液中分离出来，可与含α5β1和αv的整合素相互作用。我们之前表明，LCT可抑制人脑微血管内皮细胞的黏附、迁移、增殖和管状结构形成。为了评估LCT对眼部血管生成的抑制作用，我们在LCT存在的情况下培养主动脉和脉络膜外植体，并分析LCT对小鼠CNV模型中CNV以及氧诱导视网膜病变模型中视网膜新生血管形成的影响。我们的数据表明，在这些模型中单次注射LCT可有效减少CNV和视网膜新生血管形成。-蒙塔萨尔，F.，达尔什，M.，布莱佐，A.，奥古斯汀，S.，科纳尔，J.-B.，米利特，A.，埃拉耶布，M.，萨赫勒，J.-A.，勒奥-勒戈齐戈，A.，森纳劳布，F.，马拉基，N.，梅萨迪，E.，吉约诺，X. 勒贝菌素，一种C型凝集素，可抑制脉络膜和视网膜新生血管形成。
