Blockade of Platelet-Derived Growth Factor Signaling Inhibits Choroidal Neovascularization and Subretinal Fibrosis in Mice
Blockade of Platelet-Derived Growth Factor Signaling Inhibits Choroidal Neovascularization and Subretinal Fibrosis in Mice
复制标题
DOI：
10.3390/jcm9072242
复制
发表时间：
2020-07-01
影响因子：
3.9
通讯作者：
Ishida, Susumu
中科院分区：
文献类型：
--
作者：
Liu, Ye;Noda, Kousuke;Ishida, Susumu
新生血管性年龄相关性黄斑变性（nAMD）在世界范围内导致严重的视力丧失，其特征在于脉络膜新生血管（CNV）和纤维化的形成。在本研究中，我们的目的是研究阻断血小板衍生生长因子受体β（PDGFR-β）对激光诱导的小鼠CNV模型中脉络膜新生血管和纤维化形成的影响。首先，证实了PDGFR-β在CNV病变中的存在。玻璃体内注射PDGFR-β中和抗体显著减少CNV和视网膜下纤维化的大小。此外，视网膜下高反射物质（SHRM），OCT上的一个标志性特征，作为nAMD患者视网膜下纤维化形成的风险因素，也受到PDGFR-β阻断剂的抑制。此外，在CNV形成期间，周细胞大量募集到CNV病变，然而，PDGFR-β的阻断显著减少周细胞募集。此外，PDGF-BB刺激增加了大鼠视网膜周细胞系R-rPCT 1的迁移，这被PDGFR-β的中和所消除。这些结果表明，PDGFR-β的阻断通过抑制周细胞迁移来减弱激光诱导的CNV和纤维化。
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-beta (PDGFR-beta) on the formation of choroidal neovascularization and fibrosis in the laser-induced CNV model in mice. Firstly, the presence of PDGFR-beta in CNV lesions were confirmed. Intravitreal injection of PDGFR-beta 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-beta blockade. Furthermore, pericytes were abundantly recruited to the CNV lesions during CNV formation, however, blockade of PDGFR-beta 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-beta. These results indicate that blockade of PDGFR-beta attenuates laser-induced CNV and fibrosis through the inhibition of pericyte migration.