Antagonist of nucleolin, N6L, inhibits neovascularization in mouse models of retinopathies. Issue 4 (5th March 2020)

• Record Type: Journal Article
• Authors: Darche, Marie; Cossutta, Mélissande; Caruana, Laure; Houppe, Claire; Gilles, Maud‐Emmanuelle; Habert, Damien; Guilloneau, Xavier; Vignaud, Lucile; Paques, Michel; Courty, José; Cascone, Ilaria
• Is Part Of: FASEB journal. Volume 34:Issue 4(2020)
• Page Start: 5851
• Page End: 5862
• Publication Date: 2020-03-05
• Subjects: angiogenesis -- choroidal neovascularization (CNV) -- oxygen‐induced retinopathy (OIR) -- vascular endothelial growth factor (VEGF) -- nucleolin; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201901876R
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: Retinal vascular diseases (RVD) have been identified as a major cause of blindness worldwide. These pathologies, including the wet form of age‐related macular degeneration, retinopathy of prematurity, and diabetic retinopathy are currently treated by intravitreal delivery of anti‐vascular endothelial growth factor (VEGF) agents. However, repeated intravitreal injections can lead to ocular complications and resistance to these treatments. Thus, there is a need to find new targeted therapies. Nucleolin regulates the endothelial cell (EC) activation and angiogenesis. In previous studies, we designed a pseudopeptide, N6L, that binds the nucleolin and blocks the tumor angiogenesis. In this study, the effect of N6L was investigated in two experimental models of retinopathies including oxygen‐induced retinopathy (OIR) and choroidal neovascularization (CNV). We found that in mouse OIR, intraperitoneal injection of N6L is delivered to activated ECs and induced a 50% reduction of pathological neovascularization. The anti‐angiogenic effect of N6L has been tested in CNV model in which the systemic injection of N6L induced a 33% reduction of angiogenesis. This effect is comparable to those obtained with VEGF‐trap, a standard of care drug for RVD. Interestingly, with preventive and curative treatments, neoangiogenesis is inhibited by 59%. Our results have potential interest in the development of new therapies targeting other molecules than VEGF for RVD.