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。在老年性黄斑变性(ARMD)和糖尿病视网膜病变中观察到的视网膜和脉络膜新生血管(NV)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NV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RPE分泌血管内皮细胞生长因子的有效诱导剂。由于其他相关的生长因子没有作用，所以转化生长因子-β的作用是特定的，并且转化生长因子-β的作用被转化生长因子-b受体II抗体所中和。RT-PCR法检测到121、165和189个氨基酸亚型的血管内皮生长因子mRNA的表达，并受转化生长因子-β的上调。通过丝裂原活化蛋白激酶的特异性抑制剂和Northern印迹分析，我们发现转化生长因子-b通过MAPK和Smad途径激活血管内皮生长因子的转录。转化生长因子-β对视网膜色素上皮中血管内皮生长因子表达的调节强烈提示转化生长因子-β在视网膜病变相关的新生血管形成中起重要作用。

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. Retinal and Choroidal neovascularization (NV), observed during age related macular degeneration (ARMD) and diabetic retinopathy, 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 choroidal neovascularization. Since vascular endothelial growth factor (VEGF) is associated with NV, we have examined the role of RPE in VEGF expression. TGF-b is found to be the potent inducer of VEGF secretion by RPE. Effects of TGF-b are specific since other related growth factors had no effects, and TGF-b effects are neutralized by TGF-b receptor II antibody. RT-PCR analyses indicated the expression of 121,165 and 189 aa isoforms of VEGF mRNA, which are up regulated by TGF-b. By using specific inhibitors of mitogen activated protein kinases and Northern blot analyses, we found that TGF-b activate VEGF transcription through MAPK and smad pathways. Regulation of the expression of VEGF in RPE by TGF-b strongly suggests an important role for TGF-b in neovascularization associated with retinal disorders.