CONTROL OF CORNEAL HYDRATION AND TRANSPARENCY

控制角膜水合和透明度

• 批准号: 3255413
• 负责人: MICHAEL V RILEY
• 金额: $ 18.47万
• 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/3255413
• 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.

该研究旨在调查两种模型， 角膜内皮的应力，并建立一个 定量的基础上的离子传输机制的性质， 该细胞层负责维持角膜水合作用 和透明度。 紫外线对角膜影响的研究 内皮细胞将试图确定什么是主要的网站， 导致角膜水合作用增加的损伤， 内皮外观的变化。 据推测 一种氧化机制，由自由基的形成引起， 吸收高能光子后的自由基， 对酶或膜蛋白和脂质的损害。 结构 随后的变化可能是由于细胞骨架的改变， 元素或释放趋化因子， 粘附在内皮上的白细胞的侵入。 该假设将通过评估代谢变化进行检验， 紫外线照射和抗氧化剂和 解毒或保护酶对角膜的紫外线反应。 确定结构变化的性质和起源将 需要通过许多显微镜技术进行检查， 炎症反应的修饰，以及体外系统 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。 是 假设内皮细胞受到疾病的损害， 降低有效性或能力的方式 防御或维护机制，如泵或 屏障功能更容易受到随后的损害。 的 高血糖对山梨醇浓度的影响， 将测量肌醇和肌醇代谢，因为这些 可调节蛋白激酶和Na+-K+ ATP酶活性， 将跟踪内皮形态学和细胞模式以检测 削弱屏障特性。 附加应力和 醛糖还原酶的抑制剂将用于确定关键位点 的损害。 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 为评估假设的机制提供可靠的数据。