Role of Retinal Pigment Epithelium In Retinal Disorders

视网膜色素上皮（RPE）是存在于眼睛中的视网膜和脉络膜之间的单层细胞，对于视网膜的正常功能至关重要。视网膜的许多炎性、感染性和其它疾病与RPE的变性和/或功能障碍有关。我们已经开发了一种人RPE细胞培养系统，并以此为模型来研究RPE在视网膜疾病的病理生理学中的各种作用。我们将注意力集中在转化生长因子-β（TGF-β）上，因为TGF-β参与增殖性、炎症性和感染性病因的视网膜疾病。视网膜和脉络膜新生血管形成（CNV）是导致视力损害的主要原因，在年龄相关性黄斑变性（ARMD）和与视网膜脱离相关的增殖性玻璃体视网膜病变（PVR）中观察到。TGF-β在玻璃体、视网膜和RPE中的高表达与视网膜纤维化和CNV密切相关。然而，视网膜驻留细胞TGF-β的来源和产生尚不清楚。我们已经研究了各种细胞因子和其他介质在调节RPE表达TGF-β中的作用。我们的研究结果表明，干扰素（IFN）-g，增强TGF-β 1，但抑制TGF-β 2生产的差异作用。有趣的是，其他炎症介质，如肿瘤坏死因子（TNF）-α和白细胞介素-1增强TGF-β 1和TGF-β 2的分泌。通过实时和常规RT-PCR方法进行的mRNA分析证实了这些观察结果。IFN-g对TGF-β 1和TGF-β 2的对比效应揭示了TGF-β 1和TGF-β 2在视网膜疾病的病理生理学中可能的差异作用。TGF-β 1和TGF-β 2及其受体在视网膜疾病中的作用还有待进一步研究。 我们正在评估干扰素-β的作用和表达，它作为一种抗病毒，抗炎剂，在视网膜和脉络膜疾病中起着至关重要的作用。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液组织屏障。在人脉络膜成纤维细胞（HCHF）中，IFN-γ诱导IFN-β的分泌，其通过TNF-α的协同作用显著增强。通过IFN-γ和TNF-α处理，人RPE细胞不分泌IFN-β。白细胞介素和生长因子对HCHF和RPE细胞产生IFN-β没有影响。实时和常规RT-PCR方法显示IFN-γ和TNF-α处理的HCHF中IFN-β mRNA的表达增强。由脉络膜细胞产生的IFN-β可以在炎症条件期间起保护脉络膜脉管系统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.