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: 3263266
• 负责人: DAVID A NEWSOME
• 金额: $ 12.37万
• 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/3263266
• 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.

与年龄和玻璃膜疣相关的黄斑变性是主要的 美国老年人严重视力丧失的原因 州和其他国家。 其原因和治疗方法尚不清楚。 临床病理学研究表明 Bruch 异常相关 膜带病。 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。 锌尤其 大量存在于脉络膜视网膜复合体中。 初步研究有 显示它以一种促进的方式被颜料吸收 上皮细胞，尽管确切的机制尚不清楚。 人视网膜吸收锌的机制和动力学 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来研究各层 使用或不使用阻碍、刺激物质的实验， 减少或竞争吸收。 因为锌是酶的辅助因子，参与合成 细胞外基质分子，特别是糖复合物 与布鲁赫膜有关，我们将研究其影响 不同锌浓度对这些产品生产的影响 分子。 Some extracellular matrix molecules play important 在色素上皮与布鲁赫正常粘附中的作用 膜，被玻璃疣、色素上皮中断 脱离，以及黄斑变性的其他变化。 使用 我们采用差示萃取和亲和色谱程序 计划研究糖复合物的相互作用特性 与布鲁赫膜的其他结构大分子。 锌也是酶的辅助因子，参与维持 细胞完整性，例如超氧化物歧化酶。 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作用的理解 正常视网膜色素上皮的代谢 特别是关于细胞外基质的合成 分子和跨上皮运输，并且应该证明相关 诸如黄斑变性等临床上重要的病症。