,.
Invest Ophthalmol Vis Sci. 2020 Jul 1;61(8):30. doi: 10.1167/iovs.61.8.30.
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).
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.
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.
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.
本研究旨在探讨 CD93 和 Multimerin-2 在三种脉络膜新生血管（CNV）模型中的作用，并评估它们在年龄相关性黄斑变性（AMD）新生血管进展中的作用。
通过显微镜方法分析从 AMD 患者手术中收集的脉络膜新生血管膜。使用 CD93 敲除小鼠模型进行激光诱导的 CNV 小鼠模型和脉络膜发芽试验（CSAs）。开发了一种原始的血管生成体外 CSA，使用来自人类供体的脉络膜组织。
与健康脉络膜内皮细胞相比，AMD 患者的过度增殖脉络膜内皮细胞（EC）表达高水平的 CD93，Multimerin-2 沿脉络膜新生血管大量沉积。CD93 敲除小鼠在激光光凝后表现出明显减少的新生血管化，并且它们的脉络膜 EC 在体外血管生成测定中显示出减少的产生芽的能力。此外，能够阻碍 CD93/Multimerin-2 相互作用的抗体的存在减少了人类 CSA 中的血管发芽。
我们的结果表明，CD93 及其与 Multimerin-2 的相互作用在脉络膜病理性血管生成中发挥重要作用，为治疗新生血管 AMD 提供了新的可能性。
