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: 3264156
• 负责人: HERBERT E WHITELEY
• 金额: $ 10.82万
• 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/3264156
• 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.

这项提案的主要目标是调查 发育不良视网膜形态发生的发病机制， 利用这种情况下的优秀动物模型 表现为一种持续可重现的疾病形式 作为一种可遗传疾病发生在英国斯普林格猎犬身上 狗。这些研究直接关系到国家 《视力研究--国家计划》中所述的眼科研究所(1983- 1987)，其中建议对动物模型进行研究 患有发育和遗传性视网膜疾病的人 明确的生化缺陷和致病机制 给予高度优先的地位。 关键病变过程始于受影响的犬。 妊娠49天到50天之间的胎儿，双边影响 背侧乳头状视网膜。它的特点是有一个缺口状的 感觉性视网膜的拐点作为其外部限制膜， 外界膜失焦，组织紊乱 视网膜下腔内神经母细胞的增殖， 褶皱和花环的形成，并最终形成局部视网膜 脱离视网膜色素上皮细胞。合并后的 将使用形态和生化方法来评估 细胞表面改变在视网膜异型增生中的作用。我们会 评估细胞间连接的作用，特别是在 外界膜，正常和发育不良 用定量冷冻断裂的方法进行形态发生 方法论。此外，膜结构和膜结构的变化 将通过检查膜内成分来确定成分 颗粒(IMP)的分布，并通过使用纤毛膜，一种聚烯 能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 也要接受评估。细胞表面糖偶联物也是 对正常的细胞间黏附、迁移和 沟通。我们将检查角色，时间或 神经细胞黏附分子和其他分子的形态变化 糖偶联物可能在发育不良的形态发生中起作用。这 预计该项目将为该单元的作用提供新的见解 正常和异常的表面和膜成分 发育过程。