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REGENERATION OF CORNEAL ENDOTHELIUM

角膜内皮的再生

基本信息

批准号：
3256551
负责人：
DENIS J GOSPODAROWICZ
金额：
$ 24.53万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
1977
资助国家：
美国
起止时间：
1977-12-01 至 1992-11-30
项目状态：
已结题

项目摘要

DESCRIPTION (applicant's abstract): The long term objectives are to determine the role of fibroblast growth factors (FGF) in the control of the proliferation and differentiation of the various ocular cell types which are sensitive to it and that of the newly discovered vascular endothelial cell growth factor (VEGF) in the control of proliferation and permeability of retina derived capillary endothelial (RCE) cells. The applicant would analyze whether transfection of iris melanocytes, RPE cells, and RCE cells, with bFRG cDNA expression vector could lead to their autonomous proliferation and ultimate transformation into neoplastic cells. Using both types of transfected cell types, he would first analyze whether bFGF acts intracellularly (as most oncogene products do) or needs to be released by the cells in order to interact with exposed cell surface receptors. Since cell transformation can be the direct result of oncogene expression, the applicant would analyze in transfected cells whether constitutive expression of c fos, and c myc oncogenes can be observed. He would initiate studies on the expression in ocular tissue of VEGF and study its possible participation in proliferative disorders occurring during diabetic retinopathy. To determine if expression of the VEGF gene or FGF gene had any effect during ontogeny, the applicant would inject AHR viruses containing those genes into avial embryos at different stages of development and analyze the occurrence of developmental abnormalities or tumors with the time of injection in ocular tissues. He would study the expression of VEGF in tissue and cells derived from the ocular system. If expressed, VEGF could play a role in controlling developmental processes. He would analyze the ability of VEGF to control events related to the angiogenic process in RCE cells. This includes its chemotactic activity and its ability to stimulate plasminogen activator and collagenase, while repressing plasminogen inhibitor activity. Finally the receptor for VEGF would be defined.

描述(申请人摘要)：长期目标是确定成纤维细胞生长因子在控制血管内皮细胞生长中的作用不同类型眼细胞的增殖和分化对它和新发现的血管内皮细胞的敏感细胞生长因子(VEGF)对细胞增殖和通透性的控制视网膜来源的毛细血管内皮细胞。申请者将会分析虹膜黑素细胞、RPE细胞和RCE细胞，携带bFRG基因的表达载体可导致其自主性增殖并最终转化为肿瘤细胞。vbl.使用这两种类型的转基因细胞类型，他都会首先分析是否有bFGF 作用于细胞内(就像大多数癌基因产品一样)或需要释放通过细胞与暴露的细胞表面受体相互作用。由于细胞转化可能是癌基因表达的直接结果，申请者将在转基因细胞中分析是否构成可观察到c-fos、c-myc癌基因表达。他会的血管内皮生长因子在眼组织中表达的初步研究可能参与糖尿病期间发生的增殖性疾病视网膜病变。以确定血管内皮生长因子基因或成纤维细胞生长因子基因的表达是否具有在个体发育过程中的任何影响，申请人将注射AHR病毒将这些基因导入不同阶段的禽类胚胎中发展和分析发生发育异常或肿瘤与眼组织注射时间有关。他会研究血管内皮生长因子在眼部组织和细胞中的表达如果表达的血管内皮生长因子可能在控制发育过程中发挥作用。他将分析血管内皮生长因子控制与 RCE细胞的血管生成过程。这包括其趋化活性。以及其刺激纤溶酶原激活物和胶原酶的能力，而抑制纤溶酶原抑制物活性。最后是血管内皮生长因子受体会被定义为。