DEGENERATION AND REGENERATION IN THE MAMMALIAN RETINA

哺乳动物视网膜的退化和再生

• 批准号: 3256493
• 负责人: DON H ANDERSON
• 金额: $ 20.38万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-09-01 至 1995-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3256493
• 关键词: cats; cell cell interaction; cell cycle; cell type; cellular pathology; confocal scanning microscopy; disease /disorder model; extracellular matrix; fibroblast growth factor; histochemistry /cytochemistry; human tissue; immunochemistry; integrins; lectin; miniature swine; protein biosynthesis; protein structure function; receptor expression; retina; retina degeneration; retinal pigment epithelium; rod cell; tissue /cell culture; transforming growth factors; visual photoreceptor; vitreous body; western blottings; wound healing

When the retina is separated (detached) from the overlying monolayer of retinal pigment epithelium (APE) experimentally or as a consequence of injury, degenerative and proliferative changes occur in specific retinal cell types. When the retina is reapposed (reattached) to the RPE surface, the photoreceptor-RPE interface undergoes a significant degree of cellular "remodeling". In these experiments the detachment/ reattachment model will be used in a range of investigations designed to enhance our understanding of the retina's cellular response to, and recovery from, injury. 1. The relationship between photoreceptor outer segment degeneration, regeneration, and the integrity of the interphotoreceptor matrix (IPM) will be studied using the experimental retinal detachment model. A combination of immunochemical and lectin cytochemical techniques will be used to assess changes in specific [PM domains and components, and their relationship to retinal recovery. 2. Members of the Integrin family of adhesion receptors mediate the attachment of cells to extracellular matrix molecules. Integrins have been implicated in RPE cell anchorage to Bruch's membrane, in retina-APE adhesion, and in vitreoretinal adherence. A.) Specific integrins will be identified at three key retinal locations: the photoreceptor-RPE interface, Bruch's membrane, and the vitreoretinal border. B.) Integrins expressed by RPE cells in vivo will be compared to those expressed by RPE cells at various stages of differentiation in vitro. C.) Changes in integrin types and levels of expression will be compared in the normal, detached, and reattached retinas. 3. Transforming growth factor-beta (TGF-B) and fibroblast growth factors (FGF) are known to be present in the retina, however their functions are unknown. We will examine the roles of these two factors in the context of experimental retinal detachment/reattachment. We will identify: A.) Cellular and extracellular sites within the normal retina where these factors are located; B.) Modifications in their levels and/or distributions in the detached and reattached retina; C.) The retinal cell types that have receptors for these molecules; and D.) The effect(s) of exogenous TGF-B on intraretinal proliferation and interphotoreceptor matrix biosynthesis in vivo.

当视网膜脱离（脱离）时， 视网膜色素上皮细胞（APE）单层实验或作为 损伤、退行性和增殖性变化的结果 发生在特定的视网膜细胞类型中。 当视网膜复位后 光感受器-RPE界面 经历显著程度的细胞“重塑”。 在这些 分离/再附着模型将被用于实验中， 一系列调查，旨在提高我们的理解， 视网膜细胞对损伤的反应和恢复。 1.光感受器外节 退化，再生和完整性 感光细胞间基质（IPM）将使用 实验性视网膜脱离模型 的组合 免疫化学和凝集素细胞化学技术将用于 评估特定[项目管理领域和组成部分]的变化， 与视网膜恢复的关系 2.粘附受体的整联蛋白家族的成员介导粘附分子的粘附。 细胞与细胞外基质分子的附着。 整合素 与RPE细胞在Bruch膜上的锚定有关， 视网膜-APE粘附和玻璃体视网膜粘附。 A.）特异性整合素将在三个关键的视网膜 位置：光感受器-RPE界面，Bruch膜，和 玻璃体视网膜边缘 B.）将比较由RPE细胞在体内表达的整合素与 RPE细胞在不同分化阶段表达的那些 体外 C.）的整合素类型和表达水平的变化将是 与正常视网膜脱离视网膜复位视网膜相比 3.转化生长因子-β（TGF-β）和成纤维细胞生长 已知FGF因子（FGF）存在于视网膜中，然而它们的 功能不明。 我们将研究这两个角色 实验视网膜病变背景下的因素 分离/再附着。 我们将确定： A.）正常视网膜内的细胞和细胞外位点， 这些因素的位置， B.）修改其水平和/或分布， 视网膜脱离复位; C.）的具有这些分子受体的视网膜细胞类型; 和 D.）外源性TGF-β对视网膜内增殖的影响 和体内光感受器间基质的生物合成。