CELL-CELL INTERACTIONS IN DYSPLASTIC RETINAL MORPHOGEN

发育不良的视网膜形态发生过程中的细胞间相互作用

• 批准号: 3264160
• 负责人: HERBERT E WHITELEY
• 金额: $ 10.02万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 1991-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3264160
• 关键词: cell adhesion; cell migration; cellular pathology; congenital eye disorder; disease /disorder model; dogs; electron microscopy; embryo /fetus; embryo /fetus cell /tissue; freeze etching; histology; intercellular connection; mammalian embryology; membrane activity; membrane structure; microscopy; receptor; retina detachment; retina disorder; retinal pigment epithelium; retinaldehyde

The major objectives of this proposal are to investigate pathogenetic mechanisms of dysplastic retinal morphogenesis, taking advantage of an excellent animal model of this condition represented by a consistently reproducible form of the disorder occurring as a heritable disease in the English Springer Spaniel dog. These studies relate directly to the goals of the National Eye Institute as stated in Vision Research--A National Plan (1983- 1987) in which it is recommended that the study of animal models with developmental and hereditary disorders of the retina to definite biochemical defects and pathogenetic mechanisms be given high priority. The critical lesion process has its inception in affected canine fetuses between 49 and 50 days of gestation, bilaterally affecting the dorsal peripapillary retina. It is characterized by a notch-like inflexion of the sensory retina as its outer limiting membrane, focal loss of the outer limiting membrane, disorganized proliferation of neuroblasts within the subretinal space, the formation of folds and rosettes, and eventual local retinal detachment form retinal pigment epithelial cells. A combined morphologic and biochemical approach will be used to evaluate the role of cell surface changes in retinal dysplasia. We will evaluate the role of intercellular junctions particularly at the external limiting membrane, in normal and dysplastic morphogenesis, by using quantitative freeze-fracture methodology. In addition, changes in membrane structure and composition will be identified by examination of intramembranous particle (IMP) distribution and by the use of filipin, a polyen antibiotic capable of binding to cholesterol within membranes. Changes in intercellular junctions or membrane structure may lead to abnormalities in cell proliferation of cell death, which will also be evaluated. Cell surface glycoconjugates are also important for normal cell-cell adhesion, migration, and communication. We will examine the role, temporal or topographical changes in neural-cell adhesion molecules and other glycoconjugates may have in dysplastic morphogenesis. This project is expected to add new insight into the role of the cell surface and membrane component in normal and aberrant developmental processes.

该提案的主要目标是调查 发育不良的视网膜形态发生的发病机制， 利用这种情况的优秀动物模型 以一致可重复的疾病形式为代表 在英国史宾格犬中作为遗传性疾病发生 狗。 这些研究与国家的目标直接相关 眼科研究所在《视力研究——国家计划》（1983- 1987）其中建议动物模型的研究 患有视网膜发育和遗传性疾病 明确的生化缺陷和发病机制 给予高度优先考虑。 严重病变过程在受影响的犬身上开始 妊娠 49 至 50 天之间的胎儿，双侧影响 背侧视乳头周围视网膜。 其特点是有一个缺口状 感觉视网膜的弯曲作为其外界膜， 外界膜局灶性缺失，紊乱 神经母细胞在视网膜下腔内增殖， 形成褶皱和玫瑰花结，最终形成局部视网膜 视网膜色素上皮细胞脱离形成。 一个组合 将使用形态学和生化方法来评估 细胞表面变化在视网膜发育不良中的作用。 我们将 评估细胞间连接的作用，特别是在 外界膜，正常和发育异常 形态发生，通过使用定量冷冻断裂 方法论。 此外，膜结构的变化 成分将通过检查膜内来鉴定 颗粒（IMP）分布和通过使用菲律宾，一种多烯 能够与膜内胆固醇结合的抗生素。 细胞间连接或膜结构的变化可能 导致细胞增殖异常甚至细胞死亡， 也进行评价。 细胞表面糖复合物也 对于正常的细胞间粘附、迁移和 沟通。 我们将检查角色，时间或 神经细胞粘附分子和其他分子的拓扑变化 糖缀合物可能具有发育不良的形态发生。 这 该项目预计将为细胞的作用提供新的见解 正常和异常的表面和膜成分 发展过程。