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CD146 as a promising therapeutic target for retinal and choroidal neovascularization diseases.
- Source :
-
Science China. Life sciences [Sci China Life Sci] 2022 Jun; Vol. 65 (6), pp. 1157-1170. Date of Electronic Publication: 2021 Oct 29. - Publication Year :
- 2022
-
Abstract
- Blood vessel dysfunction causes several retinal diseases, including diabetic retinopathy, familial exudative vitreoretinopathy, macular degeneration and choroidal neovascularization in pathological myopia. Vascular endothelial growth factor (VEGF)-neutralizing proteins provide benefits in most of those diseases, yet unsolved haemorrhage and frequent intraocular injections still bothered patients. Here, we identified endothelial CD146 as a new target for retinal diseases. CD146 expression was activated in two ocular pathological angiogenesis models, a laser-induced choroid neovascularization model and an oxygen-induced retinopathy model. The absence of CD146 impaired hypoxia-induced cell migration and angiogenesis both in cell lines and animal model. Preventive or therapeutic treatment with anti-CD146 antibody AA98 significantly inhibited hypoxia-induced aberrant retinal angiogenesis in two retinal disease models. Mechanistically, under hypoxia condition, CD146 was involved in the activation of NFκB, Erk and Akt signalling pathways, which are partially independent of VEGF. Consistently, anti-CD146 therapy combined with anti-VEGF therapy showed enhanced impairment effect of hypoxia-induced angiogenesis in vitro and in vivo. Given the critical role of abnormal angiogenesis in retinal and choroidal diseases, our results provide novel insights into combinatorial therapy for neovascular fundus diseases.<br /> (© 2021. Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature.)
- Subjects :
- Animals
CD146 Antigen
Humans
Hypoxia
Neovascularization, Pathologic drug therapy
Vascular Endothelial Growth Factor A metabolism
Choroid Diseases complications
Choroidal Neovascularization drug therapy
Choroidal Neovascularization etiology
Choroidal Neovascularization pathology
Retinal Diseases metabolism
Retinal Neovascularization drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1869-1889
- Volume :
- 65
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Science China. Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 34729700
- Full Text :
- https://doi.org/10.1007/s11427-021-2020-0