Migration and proliferation of human retinal pigment epithelium

PDGF-C和PDGF-D是人视网膜色素上皮细胞（RPE）中表达的主要亚型。功能活性PDGFR-和-主要在顶膜表达。PDGF-BB、-CC、-DD显著增加增殖，而PDGF-BB、-AB和-DD显著增加细胞迁移，表明在RPE病理生理学中的关键作用。促炎细胞因子混合物（TNF/IL-1/IFN）通过诱导细胞凋亡和破坏细胞骨架和紧密连接来消除PDGF诱导的增殖和迁移。进一步的研究表明，单独的IFN显著抑制人胎儿RPE（hfRPE）增殖，这被JAK抑制剂I显著阻断，而I型IFN、IFN和IFN在相同的培养条件下不影响hfRPE增殖。将IFN添加至基底浴而非顶端浴显著增加了跨越hfRPE单层的Jv。与hfRPE相反，促炎细胞因子混合物和IFN本身刺激脉络膜细胞的增殖。这些发现表明促炎细胞因子，特别是IFN，在克服视网膜/RPE/脉络膜界面处的RPE的局部增殖/伤口愈合反应中的复杂作用。

PDGF-C and -D are the major isoforms expressed in human retinal pigment epithelium (RPE). Functionally active PDGFR-α and -β are mainly expressed at the apical membrane. PDGF-BB, -CC, -DD significantly increased proliferation while PDGF-BB, -AB and -DD significantly increased cell migration, suggesting a critical role in RPE pathophysiology. A pro-inflammatory cytokine mixture (TNFα/IL-1β/IFNγ) abrogated PDGF-induced proliferation and migration by inducing apoptosis, and by disrupting the cytoskeleton and tight junctions. Further study demonstrated that IFNγ alone significantly inhibited human fetal RPE (hfRPE) proliferation, which was significantly blocked by JAK inhibitor I, while Type I IFN, IFNα and IFNβ did not affect hfRPE proliferation under the same culture conditions. Addition of IFNγ to the basal, but not the apical bath significantly increased Jv across hfRPE monolayer. In contrast to hfRPE, the proinflammatory cytokine mixture, and IFNγ by itself, stimulated the proliferation of choroidal cells. These findings suggest a complex role of pro-inflammatory cytokines, particularly IFNγ, in overcoming local proliferative/wound healing responses of RPE at the retina/RPE/choroid interface.