Liu Ye, Noda Kousuke, Murata Miyuki, Wu Di, Kanda Atsuhiro, Ishida Susumu
Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan.
J Clin Med. 2020 Jul 15;9(7):2242. doi: 10.3390/jcm9072242.
Neovascular age related macular degeneration (nAMD) leads to severe vision loss worldwide and is characterized by the formation of choroidal neovascularization (CNV) and fibrosis. In the current study, we aimed to investigate the effect of blockade for platelet derived growth factor receptor-β (PDGFR-β) on the formation of choroidal neovascularization and fibrosis in the laser-induced CNV model in mice. Firstly, the presence of PDGFR-β in CNV lesions were confirmed. Intravitreal injection of PDGFR-β neutralizing antibody significantly reduced the size of CNV and subretinal fibrosis. Additionally, subretinal hyperreflective material (SHRM), a landmark feature on OCT as a risk factor for subretinal fibrosis formation in nAMD patients was also suppressed by PDGFR-β blockade. Furthermore, pericytes were abundantly recruited to the CNV lesions during CNV formation, however, blockade of PDGFR-β significantly reduced pericyte recruitment. In addition, PDGF-BB stimulation increased the migration of the rat retinal pericyte cell line, R-rPCT1, which was abrogated by the neutralization of PDGFR-β. These results indicate that blockade of PDGFR-β attenuates laser-induced CNV and fibrosis through the inhibition of pericyte migration.
新生血管性年龄相关性黄斑变性（nAMD）在全球范围内导致严重视力丧失，其特征是脉络膜新生血管（CNV）形成和纤维化。在本研究中，我们旨在探讨阻断血小板衍生生长因子受体-β（PDGFR-β）对小鼠激光诱导的CNV模型中脉络膜新生血管形成和纤维化的影响。首先，证实了CNV病变中存在PDGFR-β。玻璃体内注射PDGFR-β中和抗体可显著减小CNV的大小和视网膜下纤维化程度。此外，视网膜下高反射物质（SHRM）作为nAMD患者视网膜下纤维化形成的危险因素，在OCT上是一个标志性特征，PDGFR-β阻断也可抑制其形成。此外，在CNV形成过程中，周细胞大量募集到CNV病变处，然而，阻断PDGFR-β可显著减少周细胞募集。此外，血小板源性生长因子-BB（PDGF-BB）刺激可增加大鼠视网膜周细胞系R-rPCT1的迁移，而PDGFR-β的中和可消除这种迁移。这些结果表明，阻断PDGFR-β通过抑制周细胞迁移减轻激光诱导的CNV和纤维化。
