BIOLOGY OF HUMAN PIGMENT EPITHELIUM AND BRUCH'S MEMBRANE

人类色素上皮和布鲁赫膜的生物学

• 批准号: 3263270
• 负责人: DAVID A NEWSOME
• 金额: $ 11.75万
• 依托单位: TOURO INFIRMARY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1993-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3263270
• 关键词: Pongidae; aging; chemical conjugate; chromatography; collagen; electrophoresis; enzyme linked immunosorbent assay; extracellular matrix; fluorescence microscopy; free radicals; histology; histopathology; human tissue; immunofluorescence technique; immunologic techniques; metalloenzyme; microscopy; organ culture; radioassay; radioimmunoassay; radiotracer; retina degeneration; retinal pigment epithelium; superoxide dismutase; zinc

Macular degeneration associated with age and drusen is the leading cause of severe visual loss among older individuals in the United States and other countries. Its cause and treatment are unknown. Clinicopathologic studies have associated abnormalities of Bruch's membrane with the disease. Recently, in one group of patients, orally administered elemental zinc retarded the visual loss associated with macular degeneration. Zinc is particularly plentiful in the chorioretinal complex. Preliminary studies have shown it to be taken up in a facilitated fashion by the pigment epithelium, although the exact mechanism is unknown. The mechanism and kinetics of zinc uptake by the human retinal pigment epithelium using both native tissue and cultured cell layers will be investigated using radioactive zinc as a probe in experiments with and without substances that block, stimulate, reduce, or compete for uptake. Because zinc is a cofactor of enzymes involved in the synthesis of extracellular matrix molecules, particularly glycoconjugates associated with Bruch's membrane, we will investigate the effects of different zinc concentrations on the production of these molecules. Some extracellular matrix molecules play important roles in the normal adhesion of the pigment epithelium to Bruch's membrane, which is interrupted by drusen, pigment epithelial detachment, and other changes of macular degeneration. Using differential extraction and affinity chromatographic procedures we plan to investigate the interactive properties of glycoconjugates with other structural macromolecules of Bruch's membrane. Zinc is also a cofactor for enzymes involved in the maintenance of cellular integrity, such as superoxide dismustase. The effects of different concentrations of zinc on the activity of this enzyme in native and cultured pigment epithelium will be studied. These studies should improve our understanding of the role of zinc in the metabolism of the normal retinal pigment epithelium with particular respect to the synthesis of extracellular matrix molecules and transepithelial transport, and should prove relevant to such clinically important conditions as macular degeneration.

黄斑变性与年龄和玻璃疣是主要的 美国老年人严重视力丧失的原因 国家和其他国家。 其原因和治疗方法尚不清楚。 临床病理学研究表明， 膜与疾病。 最近，在一组患者中， 口服元素锌可延缓视力丧失 与黄斑变性有关 锌特别 在脉络膜视网膜复合体中大量存在 初步研究已经 显示它被颜料以一种便利的方式吸收， 上皮，尽管确切的机制尚不清楚。 人视网膜锌摄取机制及动力学研究 使用天然组织和培养细胞的色素上皮 将使用放射性锌作为探针， 有无物质的实验，这些物质可以阻断，刺激， 减少或竞争吸收。 因为锌是参与合成的酶的辅因子， 细胞外基质分子，特别是糖缀合物 与布鲁赫膜相关，我们将研究 不同的锌浓度对生产这些 分子。 一些细胞外基质分子起重要作用 在色素上皮细胞与布鲁赫的正常粘附中的作用 膜，这是中断玻璃疣，色素上皮 视网膜脱离和黄斑变性的其他变化。 使用 差示提取和亲和层析程序， 计划研究糖缀合物的相互作用性质 与布鲁赫膜的其他结构大分子结合。 锌也是一种酶的辅助因子，参与维持 细胞完整性，如超氧化物歧化酶。 的影响 不同浓度的锌对该酶活性的影响 将研究天然和培养的色素上皮。 这些研究应该提高我们对锌的作用的理解 在正常视网膜色素上皮细胞的代谢中， 特别是细胞外基质的合成 分子和跨上皮转运，并应证明相关 黄斑变性等重要的临床疾病