Role of Retinal Pigment Epithelium In Retinal Disorders

视网膜色素上皮(RPE)是视网膜和眼部脉络膜之间的单层细胞，对视网膜的正常功能至关重要。许多炎症性、感染性和其他视网膜疾病都与RPE的退化和/或功能障碍有关。我们已经开发了一个人类RPE细胞培养系统，并将其作为一个模型来研究RPE在视网膜疾病的病理生理学中的各种作用。由于转化生长因子-β参与了增生性、炎症性和感染性视网膜疾病，因此我们将注意力集中在转化生长因子-β。在老年性黄斑变性(ARMD)和增殖性玻璃体视网膜病变(PVR)合并视网膜脱离时观察到的视网膜和脉络膜新生血管(CNV)是导致视力损害的主要原因。转化生长因子-β在玻璃体、视网膜和RPE中的高表达与视网膜纤维化和新生血管的形成密切相关。然而，视网膜驻留细胞产生转化生长因子-β的来源和产生尚不清楚。我们研究了各种细胞因子和其他介质在RPE调节转化生长因子-β表达中的作用。我们的结果表明干扰素-g的作用不同，它促进了转化生长因子-β1的产生，但抑制了转化生长因子-β2的产生。有趣的是，其他炎症介质，如肿瘤坏死因子和白介素1，促进了转化生长因子-β1和转化生长因子-β2的分泌。这些观察结果得到了Real-Time和常规RT-PCR方法的信使核糖核酸分析证实。干扰素-β对转化生长因子-β1和转化生长因子-β2的对比作用为揭示转化生长因子-β1和转化生长因子-β2在视网膜疾病病理生理过程中可能的不同作用提供了新的线索。进一步的研究正在评估转化生长因子-β1和转化生长因子-β2及其受体在视网膜疾病中的潜在作用。 我们正在评估干扰素-β在视网膜和脉络膜疾病中的作用和表达，干扰素-β在视网膜和脉络膜疾病中发挥着重要的抗病毒、抗炎作用。越来越多的证据表明，干扰素-β通过保护血管细胞功能来防止血-组织屏障。在人脉络膜成纤维细胞(HCHF)中，干扰素-γ诱导人脉络膜成纤维细胞分泌干扰素-β，并在肿瘤坏死因子-α的协同作用下显著增强。人RPE细胞经干扰素-γ和肿瘤坏死因子-α处理后不分泌干扰素-β。白介素类和生长因子对HCHF和RPE细胞产生的干扰素-β均无影响。实时荧光定量RT-PCR和常规RT-PCR检测显示，经干扰素-γ和肿瘤坏死因子-α处理的HCHF细胞中，干扰素-β基因的表达增强。在炎症条件下，脉络膜细胞产生的干扰素-β可能起到保护脉络膜血管和血-视网膜屏障的完整性的作用。

Retinal pigment epithelium (RPE), a single layer of cells present between the retina and choroid in the eye, is vital for the normal functioning of the retina. Many of the inflammatory, infectious and other diseases of the retina are associated with the degeneration and /or dysfunction of the RPE. We have developed a human RPE cell culture system and have used this as a model to investigate the various roles of RPE in the pathophysiology of retinal disorders. We focused our attention on transforming Growth factor-beta (TGF-b), since TGF-b is involved in retinal disorders of proliferative, inflammatory and infectious etiology. Retinal and Choroidal neovascularization (CNV), observed during age related macular degeneration (ARMD) and proliferative vitreoretinopathy (PVR) associated with retinal detachments, are the leading causes of visual impairment. Elevated expression of TGF-b in vitreous, retina and RPE has been closely correlated with the retinal fibrosis and CNV. However, the sources and production of TGF-b by retinal resident cells were not clearly known. We have examined the role of various cytokines and other mediators in the regulation of the expression of TGF-b by RPE. Our results demonstrated a differential role for interferon (IFN)-g, which enhanced TGF-b1 but inhibited TGF-b2 production. Interestingly, other inflammatory mediators such as tumor necrosis factor (TNF)-alpha and interleukin-1 enhanced the secretion of both TGF-b1 and TGF-b2. These observations were corroborated by mRNA analyses by Real-time and conventional RT-PCR methods. The contrasting effects of IFN-g on TGF-b1 and TGF-b2 sheds new light on the possible differential actions of TGF-b1 and TGF-b2 in the pathophysiology of retinal diseases. Further studies are in progress to evaluate the potential role of TGF-b1 and TGF-b2 and their receptors in the retinal diseases. We are evaluating the role and expression of Interferon-beta, which plays a vital role as an antiviral, anti-inflammatory agent, in the retinal and choroidal diseases. There is increasing evidence that Interferon-beta prevents blood-tissue barrier by preserving vascular cell functions. In human choroidal fibroblast cells (HCHF), IFN-gamma induced secretion of IFN-beta, which was enhanced significantly by the synergistic action of TNF-alpha. Human RPE cells did not secrete IFN-beta by IFN-gamma and TNF-alpha treatment. Interleukins and growth factors had no effects on IFN-beta production by both HCHF and RPE cells. Real-time and conventional RT-PCR methods showed enhanced expression of IFN-beta mRNA in IFN-gamma and TNF-alpha treated HCHF. IFN-beta produced by choroidal cells may act to protect the integrity of the choroidal vasculature and blood-retinal barrier during inflammatory conditions.