CONTROL OF CORNEAL HYDRATION AND TRANSPARENCY

控制角膜水合和透明度

• 批准号: 3255418
• 负责人: MICHAEL V RILEY
• 金额: $ 17.24万
• 依托单位: OAKLAND UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-09-01 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3255418
• 关键词: NAD(H) phosphate; adenosinetriphosphatase; aldehyde reductase; antioxidants; bicarbonates; chemical hydration; chemoattractants; chromatography; cornea disorder; cornea edema; corneal endothelium; corneal epithelium; corneal stroma; cytoskeleton; diabetic ophthalmopathy; electron microscopy; electrophysiology; enzyme inhibitors; fluorescence microscopy; free radicals; glucose metabolism; glutathione; homeostasis; human tissue; hyperglycemia; inflammation; inositol; intraocular fluid; keratoplasty; laboratory rabbit; laboratory rat; lactates; light adverse effect; membrane lipids; membrane permeability; membrane proteins; membrane transport proteins; oxidation reduction reaction; peroxidation; physiologic stressor; pyridine nucleotide; radioimmunoassay; sodium potassium exchanging ATPase; sorbitol; stress; ultraviolet radiation; visual photosensitivity

The proposed research is designed to investigate two models of stress in the corneal endothelium and to establish on a quantitative basis the nature of the ion transport mechanisms in this cell layer are responsible for maintaining corneal hydration and transparency. A study of the effects of ultraviolet light on the corneal endothelium will seek to determine what is the primary site of injury that results in an increase in corneal hydration and marked changes in the appearance of the endothelium. It is postulated that an oxidative mechanism, provoked by the formation of free radicals following absorption of the high energy photons, causes damage to enzymes or membrane proteins and lipids. Structural changes that follow may result from alteration of cytoskeletal elements or from release of chemotactic factors that cause invasion of leukocytes that become attached to the endothelium. The hypothesis will be tested by assessing metabolic changes after UV exposure and the effects of changes in anti-oxidants and detoxifying or protective enzymes on the corneal response to UV. Defining the nature and origin of the structural changes will entail examination by a number of microscopy techniques, modification of the inflammatory response, and in vitro systems for testing chemotaxis and leukocyte recruitment. The diabetic study will seek in an animal model the basis for the failure of diabetic patients to withstand intraocular surgery without more severe corneal swelling than other patients. It is postulated that the endothelium is compromised by the disease in a manner which reduces the effectiveness or capacity of defensive or maintenance mechanisms, such that the pump or barrier functions are more vulnerable to subsequent insults. The effects of hyperglycaemia on the concentrations of sorbitol and inositol and upon inositol metabolism will be measured, as these may regulate protein kinase and Na+-K+ ATPase activities, and endothelial morphology and cell pattern will be followed to detect weakening of the barrier characteristics. Additional stresses and inhibitors of aldose reductase will be used to identify the key sites of damage. The study of ion transport in the endothelium will focus on the absolute values of fluxes and the extent of coupling in order to provide sound data for assessment of postulated mechanisms.

这项拟议的研究旨在调查两个模型 应激在角膜内皮细胞和建立在一个 离子输运机制的本质 这一细胞层负责维持角膜的水化 和透明度。 紫外线对角膜影响的研究 内皮细胞将寻求确定什么是主要的位置 导致角膜水化增加的损伤，并明显 内皮细胞外观的改变。这是假定的 这是一种氧化机制，由游离基的形成引发 吸收高能光子后的自由基，导致 对酶或膜蛋白和脂类的损害。结构性 随之而来的变化可能是细胞骨架的改变 或通过释放趋化因子引起的 附着于内皮细胞的白细胞的侵入。 这一假设将通过评估新陈代谢变化来检验 紫外线照射以及抗氧化剂和 角膜上的解毒或保护酶对紫外线的反应。 确定结构性变化的性质和根源将 需要通过一些显微镜技术进行检查， 炎症反应的修饰和体外系统 用于测试趋化性和白细胞募集。 糖尿病研究将在动物模型中寻找 糖尿病患者不能耐受眼内手术 没有比其他患者更严重的角膜肿胀。它是 假设血管内皮细胞受到疾病的损害 降低…的效力或能力的方式 防御性或维修性机构，使泵或 屏障函数更容易受到后续攻击。这个 高血糖对血浆山梨醇和血糖值的影响 肌醇和肌醇代谢将被测量，如下 可能调节蛋白激酶和Na+-K+-ATPase活性，并 将根据内皮细胞的形态和形态来检测 势垒特性的弱化。附加应力和 将使用醛糖还原酶抑制剂来确定关键部位 造成的损害。 血管内皮细胞离子转运的研究将集中在 通量的绝对值和耦合程度，以便 为评估假设机制提供可靠的数据。