The binding of CD93 to multimerin-2 promotes choroidal neovascularization

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number30
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume61
Issue number8
DOIs
Publication statusPublished - Jul 2020

Keywords

  • Age-related macular degeneration
  • Angiogenesis
  • Choriocapillaris
  • Neovascularization
  • Retinal degeneration

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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