ROLE OF HORMONES AND POLYOLS IN DIABETIC EYE DISEASE

我们的目标是阐明荷尔蒙在 调节糖尿病引起的血管通透性增加 和眼睛中的多元醇代谢。总的假设是 被提议的实验所检验的是糖尿病视网膜病变 是一种与醛糖还原酶相关的现象，其原因是 青春期前的糖尿病患者比青春期后的糖尿病患者少见 组织中醛糖还原酶的水平/活性增加 在青春期时服用性激素。这些实验 这些描述旨在：1)评估失衡在以下方面的作用 山梨醇/肌醇代谢在糖尿病发病机制中的作用 糖尿病引起的~(125)I-白蛋白渗透性增加 视网膜和选定的眼外血管，重点是 血管生成(肉芽组织血管)的新模型 糖尿病大鼠的皮下组织，2)研究糖尿病大鼠的皮下组织 性激素、胰岛素和其他激素在 调节糖尿病白内障的发生和发展 糖尿病引起的血管通透性增加和 不同组织中山梨醇/肌醇代谢的失衡 和形成的新的(肉芽组织)血管。 糖尿病的环境。 这项研究的重要性在于，信息 所获得的信息应提供有关 激素在糖尿病损伤发病机制中的作用 视网膜血管系统和神经细胞。这是一项新的 信息可以为新的治疗方法提供理论基础 实现我们长期目标的途径 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 在糖尿病眼病的发病机制中将提示 未来的研究是否应该侧重于努力 调整牵连的生产和/或影响 荷尔蒙作用于靶组织，以防止 并发症。演示这种动物的用途 研究人类糖尿病发病机制的模型 视网膜病将极大地加快研究进展， 不仅在阐明糖尿病的发病机制方面 视网膜病变，也在开发和测试新的治疗方法 旨在预防这种情况的方法和药物 并发症。

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.