BLOOD OCULAR TRANSPORT STUDIES IN EXPERIMENTAL DIABETES

实验性糖尿病中的眼部血液运输研究

• 批准号: 3258809
• 负责人: JOSEPH DIMATTIO
• 金额: $ 16.21万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-12-01 至 1991-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3258809
• 关键词: aminoacid transport; ascorbate; blood aqueous barrier; corneal endothelium; fluoresceins; fresh water environment; glucose transport; hyperglycemia; intraocular fluid; ion transport; ionophores; lens; passive transport; radioassay; retinal pigment epithelium; retinaldehyde; spectrometry; uvea ciliary body

Passive and carrier mediated glucose transport across ocular barriers and via intraocular epithelia in normal and streptozotocin (SZ)-diabetic animals will be studied to determine the role of insulin deficiency and hyperglycemia in the diabetic eye. In vivo kinetic studies have shown that blood-aqueous and vitreous passive (14C)-L-glucose rate constants increase within 10 days post-SZ, whereas, carrier facilitated (3H)-m-D-glucose is decreased only later (50 + days). Preliminary studies with the guinea pig (a mammalian model lacking a retinal circulation) have provided in vivo evidence suggesting that the retinal pigment epithelium (RPE) is an anatomical locus for carrier facilitation of glucose transport. Proposed in vivo studies using various sized molecular probes are designed to explore the nature of the blood-ocular diabetic passive leak in an effort aimed at correlating vitreous fluorescein studies with our SZ-diabetic studies using glucose analogs. Other in vivo studies will test vitamin E, C and Pfizer's Sorbinil usefullness in preventing the diabetic and transport changes seen. We have previously reported on in vivo glucose transport into lens and cornea of the rat and propose to extend these studies to diabetic animals. This would clarify whether glucose transport into lens and cornea is impaired in the diabetic animal. Our in vivo kinetic modelling will be expanded so that reversible transport occurs between blood-retina-vitreous compartments. In vitro studies of chamber mounted frog RPE have resulted in publications on ion transport and glucose transport. Glucose transport across the frog RPE was found to be insulin insensitive, adversely affected by elevated concentrations of glucose and not dependent on an immediate ATP energy supply or functioning ion-transport system. New studies include: mechanisms of amino acid transport with special attention to roles played by insulin and ascorbic acid, and an explorative study of pharmacology of ion and glucose transport across bullfrog RPE. Recent work with cell suspensions of bullfrog RPE have indicated carrier mediation of glucose transport not insulin dependent. This work will be extended to include RPE cells from diabetic animals aimed at studying the kinetics of glucose transport in specific diabetic cell populations. Specific binding studies with (125I)-Insulin have revealed that although insulin is not required for carrier glucose transport a specific insulin receptor is present in frog RPE membrane. Binding studies will be extended to include epithelial cells isolated from normal and diabetic rats and guinea pigs.

被动和载体介导的葡萄糖跨眼屏障和 通过正常和链霉菌素（SZ） - 糖尿病的人工上皮 将研究动物以确定胰岛素缺乏症的作用和 糖尿病眼中高血糖。 体内动力学研究表明 血液和玻璃体被动（14C）-L-葡萄糖速率增加 在SZ后10天内，载体促进（3H）-M-D-葡萄糖为 稍后减少（50 +天）。 豚鼠的初步研究 （缺乏视网膜循环的哺乳动物模型）在体内提供了 证据表明视网膜色素上皮（RPE）是 解剖基因座用于载体的葡萄糖转运。 建议的 使用各种大小分子探针的体内研究设计为 努力探索血统糖尿病性被动泄漏的性质 旨在将玻璃荧光素研究与我们的SZ糖尿病患者相关联 使用葡萄糖类似物的研究。 其他体内研究将测试维生素E， C和辉瑞在防止糖尿病和 看到的运输变化。 我们以前曾报告过体内葡萄糖进入镜头，并 大鼠的角膜并提议将这些研究扩展到糖尿病动物。 这将阐明葡萄糖转运到镜头和角膜中是否是 糖尿病动物受损。 我们的体内动力学建模将是 扩展，使得可逆运输发生在血液 - 逆转频率之间 车厢。 室内固定的青蛙RPE的体外研究已导致 关于离子运输和葡萄糖运输的出版物。 葡萄糖转运 发现整个青蛙RPE被发现是胰岛素不敏感的，受到不利影响 通过葡萄糖的浓度升高，不取决于立即的ATP 能源供应或功能性离子传输系统。 新研究包括： 氨基酸运输机制，特别注意扮演的角色 通过胰岛素和抗坏血酸，以及对药理学的探索性研究 离子和葡萄糖跨牛肉RPE。 细胞的最新工作 Bullfrog RPE的悬浮液表明葡萄糖的载体介导 转运不依赖胰岛素​​。 这项工作将扩展到包括RPE 旨在研究葡萄糖动力学的糖尿病动物的细胞 特定糖尿病细胞种群中的运输。 特定的结合研究 （125i） - 胰岛素已经显示，尽管不需要胰岛素 载体葡萄糖转运青蛙中存在特定的胰岛素受体 RPE膜。 结合研究将扩展到包括上皮细胞 从正常和糖尿病大鼠和豚鼠中分离出来。