ROLE OF HORMONES AND POLYOLS IN DIABETIC EYE DISEASE

激素和多元醇在糖尿病眼病中的作用

• 批准号: 3263004
• 负责人: JOSEPH R WILLIAMSON
• 金额: $ 27.4万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1991-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3263004
• 关键词: adenosinetriphosphatase; aldehyde reductase; angiogenesis; carbohydrate metabolism; cortisol; diabetes mellitus; diabetic cataract; diabetic retinopathy; disease /disorder model; gas chromatography mass spectrometry; hormone regulation /control mechanism; inositol; insulin; iodine; laboratory rat; luteinizing hormone; medical complication; radiotracer; sex hormones; sorbitol; steroid hormone; testosterone; vascular endothelium permeability

Our objective is to elucidate the role of hormones in modulating diabetes-induced increases in vascular permeability and polyol metabolism in the eye. The general hypothesis to be tested by the proposed experiments is that diabetic retinopathy is an aldose reductase-linked phenomenon and the reason it is much less common in pre- than in post-pubertal diabetics is that tissue levels/activity of aldose reductase are increased by sex steroids at the time of puberty. The experiments described are designed to: 1) assess the role of imbalances in sorbitol/inositol metabolism in the pathogenesis of diabetes-induced increases in 125I-albumin permeation of the retina and in selected extraocular vessels with emphasis on a new model of angiogenesis (granulation tissue vessels) in subcutaneous tissues of diabetic rats, and 2) investigate the role of sex steroids, insulin, and selected other hormones in modulating the development of diabetic cataracts as well as diabetes-induced increases in vascular permeability and imbalances in sorbitol/inositol metabolism in various tissues of the eye and in new (granulation tissue) vessels formed in the diabetic milieu. The importance of this research is that the information obtained should provide important new insights regarding the role of hormones in the pathogenesis of diabetes-induced injury to the retinal vasculature and neural elements. This new information could provide the rationale for new therapeutic approaches for implementation of our long range goal of preventing diabetic vascular disease. Delineation of the role of sex steroids, insulin, corticosteroids, and growth hormone in the pathogenesis of diabetic ocular disease will indicate whether future research should be focused on efforts to modulate the production and/or effects of the implicated hormone on target tissues in order to prevent the complications. Demonstration of the utility of this animal model for investigating the pathogenesis of human diabetic retinopathy would greatly expedite the progress of research, not only in elucidating the pathogenesis of diabetic retinopathy but also in developing and testing new therapeutic approaches and pharmacologic agents designed to prevent such complications.

我们的目标是阐明激素在 调节糖尿病诱导的血管通透性增加 和眼睛中的多元醇代谢。 一般的假设是 糖尿病性视网膜病变是一种常见的视网膜病变。 是一种与醛糖还原酶相关的现象， 在青春期前糖尿病患者中比在青春期后糖尿病患者中更不常见， 醛糖还原酶的组织水平/活性增加 在青春期时被性类固醇所影响 实验 所描述的目的是：1）评估不平衡的作用， 山梨糖醇/肌醇代谢的发病机制 糖尿病诱导的125 I-白蛋白渗透增加 视网膜和选定的眼外血管，重点是 新的血管生成模型（肉芽组织血管）， 糖尿病大鼠皮下组织，和2）研究 性类固醇，胰岛素和其他选定的激素在 调节糖尿病性白内障的发展以及 糖尿病引起的血管通透性增加， 各种组织中山梨醇/肌醇代谢不平衡 在眼睛和新的（肉芽组织）血管中形成， 糖尿病的环境 这项研究的重要性在于， 获得的信息应该提供重要的新见解， 激素在糖尿病损伤发病机制中的作用 视网膜血管和神经系统 这个新 这些信息可以为新的治疗方法提供理论依据， 实现我们长期目标的方法， 预防糖尿病血管疾病。 角色的界定 性类固醇胰岛素皮质类固醇和生长激素 糖尿病性眼病的发病机制 未来的研究是否应该集中在努力， 调节所涉物质的产生和/或影响 激素对靶组织，以防止 并发症 证明这种动物的效用 人糖尿病发病机制研究模型 视网膜病将大大加快研究的进展， 不仅可以阐明糖尿病的发病机制， 视网膜病变，而且在开发和测试新的治疗 设计用于预防这种疾病的方法和药剂 并发症