CONTROL OF CORNEAL HYDRATION AND TRANSPARENCY

这项拟议中的研究旨在研究某些生物化学物质， 和生理过程，是维持一个基本的 正常功能的角膜。 为了使组织透明， 必须在基质中保持恒定的水合水平， 需要在基质对流体的吸胀和基质对流体的吸胀之间保持平衡。 挤压穿过内皮。 这种平衡是由 内皮细胞层对水和溶质的渗透性， 能量依赖的活性离子传输过程的效率。 以来 脂质对于维持正常的渗透性和 细胞膜特性和脂蛋白酶的正常活性 复合物，可能导致角膜稳态的失败， 这些化合物的降解。 假设在正常情况下， 在体内，角膜受到持续的攻击， 氧化剂，如水状体中的H2O2和自由基， 细胞中的氧反应，并且这些反应被认为是无害的， 抗氧化剂、解毒酶和保护酶系统。 在 体外，或在可能由于 病理、老化或过度暴露于光，这些保护性 机制可能会过度延伸，允许脂质过氧化和游离 蛋白质和碳水化合物的自由基损伤， 失败 这一假设将通过测量代谢反应来检验， 关键代谢物的酶活性和氧化还原状态和浓度 角膜暴露于H2O2或UV光后。 其他不良 条件将被测试的累积效应的压力，而增加 将评估抗氧化剂或酶的保护能力。 的 这些系统的状态和它们对氧化挑战的脆弱性将 也可以在糖尿病动物中进行测量，以确定角膜问题是否 糖尿病玻璃体切除术患者遇到的问题可能是由于手术失败造成的。 流体泵的机理及其对所述条件的响应 上面也将进行检查。 穿过内皮的离子通量和阳离子 和阴离子交换过程将被测量，以确定 运输的主要离子和质子、CO2和碳的作用 脱水酶在流体运动中的作用

The proposed research is designed to investigate certain of the biochemical and physiological processes that are fundamental to the maintenance of a normally functional cornea. In order that the tissue be transparent a constant level of hydration must be maintained in the stroma and this necessitates a balance between imbibition of fluid by the stroma and its extrusion across the endothelium. This equilibrium is determined by the permeability of the endothelial cell layer to water and solutes and by the efficiency of the energy-dependent process of active ion transport. Since lipids are critical for the maintenance of both normal permeability characteristics of cell membranes and normal activity of lipoprotein enzyme complexes, it is possible that failure of corneal homeostasis may result from degeneration of these compounds. It is postulated that under normal, in vivo, circumstances the cornea is subjected to a continuous attack by oxidants, such as H2O2 in the aqueous humor and free radicals generated by oxygen reactions in the cell, and that these are rendered innocuous by anti-oxidants, detoxifying enzymes and protective enzyme systems. In vitro, or under conditions of added stress that might be due to pathologies, aging, or excessive exposure to light, these protective mechanisms may be over-extended, allowing peroxidation of lipids and free radical damage to proteins and carbohydrates, with ensuing physiological failure. This hypothesis will be tested by measuring metabolic reactions, enzyme activities and redox state and concentration of key metabolites following exposure of corneas to H2O2 or UV light. Other adverse conditions will be tested for cumulative effects of stress, while added anti-oxidants or enzymes will be assessed for protective capacities. The status of these systems and their vulnerability to oxidative challenge will also be measured in diabetic animals to determine whether corneal problems encountered in diabetic vitrectomy patients might be due to their failure. The mechanisms of the fluid pump and its response to conditions described above will also be examined. Ion fluxes across the endothelium and cation and anion exchange process will be measured in order to determine the primary ion(s) transported and the role of protons, CO2 and carbonic anhydrase in fluid movement.