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。视网膜的许多炎症性、感染性和遗传性疾病都与RPE的退化和/或功能障碍有关。我们已经开发了人类RPE细胞培养系统，并将其作为模型来研究RPE在视网膜疾病的病理生理学中的各种作用。由于转化生长因子-β与增殖性、炎症性和感染性视网膜病变有关，我们将注意力集中在转化生长因子-β。弓形虫是一种原虫，由弓形虫引起的视网膜脉络膜炎可引起视网膜炎症和坏死，是葡萄膜炎的常见病因之一。当弓形虫在体外感染RPE细胞时，我们观察到一种天然抗炎剂--转化生长因子-b的mRNA和蛋白分泌增加。这些结果表明宿主视网膜细胞与弓形虫之间的相互作用可能在视网膜脉络膜炎的发病机制中发挥积极作用。脉络膜新生血管(CNV)是老年性黄斑变性(ARMD)的主要事件之一，ARMD是老年人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脉络膜新生血管的形成密切相关。由于血管内皮生长因子(VEGF)与CNV相关，我们研究了RPE在VEGF表达中的作用。转化生长因子-β被发现是分泌血管内皮细胞生长因子的有效诱导剂。RT-PCR分析表明，存在121、165和189个氨基酸亚型的血管内皮生长因子，它们被转化生长因子-β上调。通过使用丝裂原活化蛋白激酶的特异性抑制剂，我们发现转化生长因子-b似乎通过MAPK和Smad途径在转录上激活了血管内皮生长因子。转化生长因子-β对血管内皮细胞生长因子表达的调节作用强烈提示转化生长因子-β在急性呼吸窘迫综合征新生血管中的重要作用。

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 hereditary diseases of the retina are associated with the degeneration and /or dysfunction of the RPE. We have developed 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 have focussed our attention on Transforming Growth factor-beta (TGF-b), since TGF-b is involved in retinal disorders of proliferative, inflammatory and infectious etiology. Retinochoroiditis induced by Toxoplasma gondii (T. gondii ), a protozoan parasite, infections results in inflammation and necrosis of the retina, and is one of the common causes of uveitis. When T. gondii infects RPE cells in vitro, we observed an elevated mRNA and protein secretion of TGF-b, a native anti-inflammatory agent. These results indicate interactions between host retinal cells and T. gondii that may play an active role in the pathogenesis of retinochoroiditis. Choroidal neovascularization (CNV) is one of the major events in the age related macular degeneration (ARMD), a leading cause of visual impairment in the aged population. Elevated expression of TGF-b in vitreous, retina and RPE has been closely correlated with the retinal fibrosis and choroidal neovascularization. Since vascular endothelial growth factor (VEGF) is associated with CNV, we have examined the role of RPE in VEGF expression. TGF-b is found to be the potent inducer of VEGF secretion. RT-PCR analyses indicated the presence of 121,165 and 189 aa isoforms of VEGF, which are up regulated by TGF-b. By using specific inhibitors of mitogen activated protein kinases, we found that TGF-b appears to transcriptionally activate VEGF through MAPK and smad pathway. Regulation of the expression of VEGF by TGF-b strongly suggests an important role for TGF-b in CNV in ARMD.