Migration and proliferation of human retinal pigment epi

人视网膜色素上皮细胞的迁移和增殖

• 批准号: 7322458
• 负责人: sheldon s miller
• 金额: --
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7322458
• 关键词: Migration; proliferation; human; retinal; pigment

Abnormal migration and proliferation of human retinal pigment epithelial cells are closely associated with many severe ocular diseases, such as PVR, AMD, and PDR. Various growth factors as well as cytokines are upregulated in the vitreous cavity after destruction of blood retinal barrier. The purpose of this project is to examine the effect of different growth factors as well as cytokines on the migration and proliferation of human retinal pigment epithelial cells. All PDGF isoforms (PDGF-A, -B, -C and ?D) are expressed in human fetal retinal pigment epithelial cells (hfRPE). Both of two PDGF receptors, -alpha and -beta are localized to the apical membrane on hfRPE. PDGF BB, AB and DD significantly increased the migration of hfRPE, and PDGF BB, CC and DD significantly increased proliferation. A proinflammatory cytokine cocktail composed of TNFa, IL-1beta and IFN-gama completely inhibited the stimulatory effects of fetal bovine serum as well as PDGF BB-induced migration and proliferation of hfRPE. Annexin-V-Fluos analysis showed that the inflammatory cytokine cocktail induced apoptosis in hfRPE which partially explained the inhibiton effect of inflammatory cytokine cocktail. These results may help identify a set of pathways (eg, apoptosis) potentially important for mitigating the progression of growth factor mediated retinal degenerative diseases such as PVR and AMD.

视网膜色素上皮细胞的异常迁移和增殖与PVR、AMD、PDR等严重眼部疾病密切相关。血视网膜屏障破坏后，玻璃体腔内各种生长因子以及细胞因子上调。本课题旨在研究不同生长因子及细胞因子对人视网膜色素上皮细胞迁移和增殖的影响。 所有PDGF亚型（PDGF-A、-B、-C和？D）在人胎儿视网膜色素上皮细胞（hfRPE）中表达。两种PDGF受体-α和-β都定位于hfRPE上的顶膜。PDGF BB、AB和DD显著增加hfRPE的迁移，PDGF BB、CC和DD显著增加增殖。由TNF α、IL-1 β和IFN-γ组成的促炎细胞因子混合物完全抑制胎牛血清的刺激作用以及PDGF BB诱导的hfRPE的迁移和增殖。Annexin-V-Fluos分析显示，炎性细胞因子鸡尾酒诱导hfRPE细胞凋亡，这部分解释了炎性细胞因子鸡尾酒的抑制作用。这些结果可能有助于确定一组途径（例如，细胞凋亡）可能对减缓生长因子介导的视网膜退行性疾病（如PVR和AMD）的进展至关重要。