DEGENERATION AND REGENERATION IN THE MAMMALIAN RETINA

哺乳动物视网膜的退化和再生

• 批准号: 2158338
• 负责人: DON H ANDERSON
• 金额: $ 21.2万
• 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/2158338
• 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.

当视网膜与其上的视网膜分离时 单层视网膜色素上皮(APE)实验或AS 损伤、退行性和增殖性变化的后果 发生在特定类型的视网膜细胞中。当视网膜被重新放置时 (重新连接)到RPE表面，光感受器-RPE界面 经历了相当程度的细胞“重塑”。在这些 实验分离/再附着模型将用于 一系列的调查，旨在增进我们对 视网膜对损伤的细胞反应，以及损伤后的恢复。 1.光感受器外节之间的关系 退化、再生和生命的完整性 光感受器间基质(IPM)将使用 实验性视网膜脱离模型。一种组合 免疫化学和凝集素细胞化学技术将用于 评估特定[PM域和组件及其 与视网膜恢复的关系。 2.黏附受体整合素家族成员介导 细胞与细胞外基质分子的连接。整合素 与RPE细胞锚定到Bruch膜有关，在 视网膜-类人猿粘连，玻璃体-视网膜粘连。 (A.)将在视网膜的三个关键部位识别特定的整合素 位置：光感受器-RPE界面、Bruch膜和 玻璃体视网膜边缘。 B.)RPE细胞体内表达的整合素将与 在不同分化阶段的RPE细胞表达的那些 在试管中。 (C)整合素类型和表达水平的变化将是 比较正常、脱离和复位的视网膜。 转化生长因子-β与成纤维细胞生长 已知视网膜中存在成纤维细胞生长因子(FGF)，然而其 功能未知。我们将研究这两个角色 实验性视网膜病变的相关因素 脱离/重新连接。我们将确定： (A.)正常视网膜内的细胞和细胞外位置 这些因素是有位置的； B.)对其级别和/或分布的修改 视网膜脱离和复位； (C)有这些分子受体的视网膜细胞类型； 和 D.)外源性转化生长因子-β对视网膜内增殖的影响(S) 体内光感受器间基质的生物合成。