ROLE OF RETINAL PIGMENT EPITHELIUM IN RETINAL DISORDERS

视网膜色素上皮在视网膜疾病中的作用

• 批准号: 6290126
• 负责人: CHANDRASEK N NAGINENI
• 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/6290126
• 关键词: Toxoplasma gondii; cell adhesion molecules; chorioretinitis; cytokine; enzyme induction /repression; eye infections; gel mobility shift assay; human tissue; inflammation; interferon gamma; interleukin 1; interleukin 6; nitric oxide; northern blottings; ocular toxoplasmosis; polymerase chain reaction; retina disorder; retinal pigment epithelium; tissue /cell culture; transcription factor; transforming growth factors; tumor necrosis factor alpha; uveitis

Retinal pigment epithelium (RPE), a single layer of cells present between the retina and choroid, is vital for the normal functioning of the retina. Many of the retinal diseases are caused by the disfunction of RPE. Human RPE cell cultures (HRPE) were used as a model to investigate the various roles of RPE in the pathophysiology of retinal disorders. We reported that human RPE cells upregulate mRNA levels and secrete significant quantities of IL-6, ICAM-1, GMCSF, nitric oxide and vascular endothelial growth factor in response to the stimulation by inflammatory cytokines. Toxoplasma gondii,that frequently causes retinochoroiditis in ocular toxoplasmosis,infection of HRPE induces secretion of IL-1, IL- 6, GMCSF and ICAM-1 but not nitric oxide by transcriptional activation of their genes. The secretion of these molecules by HRPE suggests that RPE plays a critical role in the immuno- pathological processes of retinal disorders. Transforming growth factor-beta (TGF-b) is involved in retinal disorders of proliferative,inflammatory and infectious etiology. Expression of TGF-b in ocular tissues is altered in age related macular degeneration, diabetic retinopathy and proliferative vitreoretinopathy. We have used primary HRPE cultures to evaluate the role of inflammatory mediators and T.gondii infection on TGF-b secretion. HRPE cells secreted TGF-b1 in a latent form while 15-40 % of secreted TGF-b2 was in a mature (active) form. IL-1 and TNF-alpha stimulated secretion of TGF- b1 and b2. Interferon-gamma stimulated secretion of TGF-b1 but inhibited secretion of TGF-b2. T. gondii infection of HRPE cells as well as treatment of HRPE cells with soluble extracts of T.gondii induced secretion of TGF-b1 and TGF-b2. TGF-b mRNA levels under these conditions correlated with the levels of secreted TGF-b suggesting a possible transcriptional regulation. TGF-b secreted by HRPE cells in response to inflammatory cytokines and T. gondii infection may play an important role in the pathophysiological processes of inflammatory and infectious diseases of the retina. - Human retinal pigment epithelial cells, age related macular degeneration, diabetic retinopathy, inflammation, cytokines, toxoplasmosis.

视网膜色素上皮（RPE）是存在于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。许多视网膜疾病都是由RPE功能障碍引起的。人RPE细胞培养物（HRPE）被用作研究RPE在视网膜疾病的病理生理学中的各种作用的模型。我们报道了人RPE细胞在炎症细胞因子刺激下上调mRNA水平并分泌大量的IL-6、ICAM-1、GMCSF、一氧化氮和血管内皮生长因子。弓形虫感染HRPE后，通过基因转录激活IL-1、IL- 6、GM-CSF和ICAM-1等细胞因子的分泌，但不诱导一氧化氮的分泌。HRPE分泌这些分子表明RPE在视网膜疾病的免疫病理过程中起关键作用。转化生长因子-β（TGF-β）参与增殖性、炎性和感染性病因的视网膜病症。在年龄相关性黄斑变性、糖尿病性视网膜病变和增生性玻璃体视网膜病变中，眼组织中TGF-β的表达改变。我们使用原代HRPE培养来评估炎症介质和弓形虫感染对TGF-β分泌的作用。HRPE细胞以潜伏形式分泌TGF-β 1，而15- 40%的分泌TGF-β 2是成熟（活性）形式。IL-1和TNF-α刺激TGF-β 1和β 2的分泌。干扰素-γ刺激TGF-β 1的分泌，但抑制TGF-β 2的分泌。T.弓形虫感染HRPE细胞以及用弓形虫可溶性提取物处理HRPE细胞诱导TGF-β 1和TGF-β 2的分泌。在这些条件下的TGF-β mRNA水平与分泌的TGF-β水平相关，表明可能的转录调节。HRPE细胞对炎性细胞因子和T.弓形虫感染可能在视网膜炎性和感染性疾病的病理生理过程中起重要作用。- 人类视网膜色素上皮细胞，年龄相关性黄斑变性，糖尿病视网膜病变，炎症，细胞因子，弓形虫病。