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The Binding of CD93 to Multimerin-2 Promotes Choroidal Neovascularization

Authors :
Tosi, Gian Marco
Neri, Giovanni
Barbera, Stefano
Mundo, Lucia
Parolini, Barbara
Lazzi, Stefano
Lugano, Roberta
Poletto, Evelina
Leoncini, Lorenzo
Pertile, Grazia
Mongiat, Maurizio
Dimberg, Anna
Galvagni, Federico
Orlandini, Maurizio
Tosi, Gian Marco
Neri, Giovanni
Barbera, Stefano
Mundo, Lucia
Parolini, Barbara
Lazzi, Stefano
Lugano, Roberta
Poletto, Evelina
Leoncini, Lorenzo
Pertile, Grazia
Mongiat, Maurizio
Dimberg, Anna
Galvagni, Federico
Orlandini, Maurizio
Publication Year :
2020

Abstract

PURPOSE. The purpose of this study was to investigate the involvement of CD93 and Multimerin-2 in three choroidal neovascularization (CNV) models and to evaluate their contribution in the neovascular progression of age-related macular degeneration (AMD). METHODS. Choroidal neovascular membranes collected during surgery from AMD patients were analyzed by microscopy methods. Laser-induced CNV mouse models and choroid sprouting assays (CSAs) were carried out using the CD93 knockout mouse model. An original ex vivo CSA of vascular angiogenesis, employing choroid tissues isolated from human donors, was developed. RESULTS. In contrast to healthy choroid endothelium, hyperproliferative choroidal endothelial cells (ECs) of AMD patients expressed high levels of CD93, and Multimerin-2 was abundantly deposited along the choroidal neovasculature. CD93 knockout mice showed a significant reduced neovascularization after laser photocoagulation, and their choroidal ECs displayed a decreased ability to produce sprouts in ex vivo angiogenesis assays. Moreover, the presence of an antibody able to hamper the CD93/Multimerin-2 interaction reduced vascular sprouting in the human CSA. CONCLUSIONS. Our results demonstrate that CD93 and its interaction with Multimerin-2 play an important role in pathological vascularization of the choroid, disclosing new possibilities for therapeutic intervention to neovascular AMD.

Details

Database :
OAIster
Notes :
application/pdf, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1234333965
Document Type :
Electronic Resource
Full Text :
https://doi.org/10.1167.iovs.61.8.30