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: 3264161
• 负责人: HERBERT E WHITELEY
• 金额: $ 10.12万
• 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 1992-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3264161
• 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; neural cell adhesion molecules; 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.

本提案的主要目的是调查 发育不良性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， 表现为一种可持续复制的疾病 作为一种遗传性疾病发生在英国史宾格猎犬身上 狗 这些研究直接关系到国家的目标， 视力研究----国家计划（1983年- 1987年），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， 给予高度重视。 关键病变过程有其开始在受影响的犬 妊娠49 - 50天的胎儿，双侧受累 背侧视乳头周围视网膜。 它的特点是一个缺口状 作为其外界膜的感觉视网膜的膜， 外界膜局灶性丧失，结构紊乱 视网膜下腔内成神经细胞的增殖， 褶皱和隆起的形成，最终局部视网膜 视网膜色素上皮细胞脱落。 组合 形态学和生化方法将用于评估 细胞表面改变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，采用定量冷冻断裂 方法论 此外，膜结构的变化和 通过检查膜内细胞来鉴定组成 颗粒（IMP）分布，并通过使用菲律宾，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 导致细胞增殖异常的细胞死亡，这将 也被评价。 细胞表面糖缀合物也是 对于正常细胞-细胞粘附、迁移和 通信 我们将研究的作用，时间或 神经细胞粘附分子和其他 糖缀合物在发育异常的形态发生中可能起作用。 这 该项目预计将增加对细胞作用的新见解 正常和异常时表面和膜成分 发展过程。