RPE TRANSEPITHELIAL TRANSPORT

RPE 跨皮转运

• 批准号: 2159418
• 负责人: DONALD A FRAMBACH
• 金额: $ 11.84万
• 依托单位: DOHENY EYE INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-11-15 至 1994-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2159418
• 关键词: acetazolamide; apical membrane; beta adrenergic agent; biological fluid transport; carbonic anhydrase inhibitors; cyclic AMP; electrophysiology; embryo /fetus tissue /cell culture; eye pharmacology; histamine; human fetus tissue; membrane permeability; membrane transport proteins; nucleotide metabolism; phosphodiesterase inhibitors; prostaglandin E; radioimmunoassay; radionuclides; receptor; retina disorder; retinal adaptation; retinal pigment epithelium; retinaldehyde; vasoactive intestinal peptide

The retinal pigment epithelium (RPE) forms a major portion of the blood retinal barrier and helps to maintain the environment required for normal retinal activity. Although disruption of the RPE blood-retinal barrier and RPE transport have been associated with clinical disease, very little is known about the precise nature of these functions. The long term goal of this research is to fully characterize the transepithelial transport and barrier properties of human RPE so that clinical disease in humans can be more completely understood, more effectively treated and, possibly, even prevented. We have developed a preparation of cultured fetal human RPE that is well suited for studies of RPE transport. Using this preparation, we have collected preliminary data which suggests that the results of the experiments we propose to do during the next grant period may lead to a better understanding and possible treatment or prevention of specific human diseases. During the next grant period, we propose: 1)to characterize cultured fetal human RPE transepithelial transport by extending Ussing chamber studies using pharmacologic probes, ion manipulation, and isotope flux studies. 2)to determine how cultured fetal human RPE transepithelial transport is modulated by intracellular cyclic AMP. 3)to determine the degree to which cultured fetal human RPE transepithelial transport may be regulated by extracellular receptors (such as those to beta adrenergic agents) and to determine the degree to which cultured fetal human RPE transepithelial transport is affected by agents (such as (IBMX) that alter intracellular cyclic AMP metabolism. 4)to incorporate measurements of trans-RPE fluid fluxes into these studies so that fluid fluxes can be measured directly rather than calculated from isotope fluxes which are subject to cumulative experimental errors.

视网膜色素上皮（RPE）形成了血液的主要部分 视网膜屏障并有助于维持正常所需的环境 视网膜活动。虽然RPE血液 - 视视屏障的破坏和 RPE运输与临床疾病有关，很少 知道这些功能的确切性质。长期目标的 这项研究是为了充分表征thransepithitial运输和 人RPE的障碍特性，使人类的临床疾病可以是 更完全理解，更有效地对待，甚至可能 阻止。 我们已经开发了培养的胎儿人RPE的准备 适用于RPE运输研究。使用此准备，我们有 收集的初步数据表明 我们建议在下一个赠款期间进行的实验可能会导致 更好地理解，可能的治疗或预防特定人类 疾病。 在下一个赠款期间，我们建议： 1）表征培养的胎儿人类RPE transepithialial运输 使用药理探针扩展室内研究，离子 操纵和同位素通量研究。 2）确定培养的胎儿人类RPE转运如何 由细胞内循环AMP调节。 3）确定培养的胎儿人类RPE transepithial的程度 运输可能由细胞外受体调节（例如 β肾上腺素能剂）并确定培养的胎儿的程度 人类RPE transepithelial运输受代理的影响（例如（IBMX） 这会改变细胞内循环AMP代谢。 4）将反射液通量的测量纳入这些研究 因此，可以直接测量流体通量，而不是根据 同位素通量会受到累积实验误差的约束。