PROTECTION OF THE EYE AGAINST OXIDATIVE DAMAGE

保护眼睛免受氧化损伤

• 批准号: 2164421
• 负责人: RICHARD C HUNT
• 金额: $ 22.57万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-06-01 至 1998-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2164421
• 关键词: X ray spectrometry; angiogenesis; angiogenesis factor; blood brain barrier; copper; diabetic retinopathy; enzyme induction /repression; fluorescent dye /probe; free radical oxygen; heme; hemopexin; histochemistry /cytochemistry; iron; laboratory rat; metal metabolism; neuroprotectants; northern blottings; oxidative stress; polymerase chain reaction; retina disorder; retinopathy of prematurity; scanning electron microscopy; superoxide dismutase; transferrin

Several retinal diseases (particularly retinopathy of prematurity, diabetic retinopathy and sickle cell retinopathy) may result from oxidative damage since all occur under conditions of oxidative stress or hemorrhage. The neural retina is a highly oxygenated tissue and a prime site for free radical generation. It also contains a high level of polyunsaturated fatty acids, prime targets for free radical peroxidation. The generation of reactive oxygen species is catalyzed by transition metals, chiefly small iron complexes, but also by copper and heme. These may result from ischemia, hemorrhage or the normal mechanism of the transport of iron across the blood-retina barrier. Because of its sensitivity to free radical damage, the retina must possess protective mechanisms. Since this tissue is separated from the circulation by a barrier cell layer, protective plasma proteins are excluded from this tissue which may, therefore, contain sites of transition metal storage and synthesize its own protective proteins. The sites of metal deposition in the retina will be determined using cytochemistry and scanning electron microscopy combined with dispersive X-ray analysis. The control of synthesis of transferrin, hemopexin and other protective proteins such as haptoglobin which binds hemoglobin and metallothionein and superoxide dismutase which quench free radicals will be studied in vivo and in vitro under various conditions using Northern blots and polymerase chain reaction to detect messenger RNA levels together with in situ hybridizations to detect the sites of synthesis. Fluorescence techniques will be used to determine whether the presence of transition metals, oxidative stress and diabetes induces free radical generation in the retina. A common factor in the above retinopathies is angiogenesis which often leads to retinal traction. The mechanism of the induction of capillary growth by reactive oxygen species may involve locally produced growth factors. The possibility that certain cells in the retina produce such substances in situations of oxidative stress will be studied and the identification of the growth factors pursued. Elucidation of the role of reactive oxygen species in the retina together with the way in which the retina protects itself should indicate how these protective mechanisms become overwhelmed in retinopathy disease.

几种视网膜疾病（特别是早产儿视网膜病变， 糖尿病视网膜病变和镰状细胞性视网膜病变）可能由以下原因引起 氧化损伤，因为所有这些都发生在氧化应激或 出血。神经视网膜是一个高度含氧的组织，是一个主要的组织。 自由基产生的场所。它还含有高水平的 多不饱和脂肪酸，自由基过氧化的主要目标。 通过过渡催化活性氧的产生 金属，主要是小的铁络合物，但也包括铜和血红素。这些 可能是由于缺血、出血或正常机制造成的 铁穿过血-视网膜屏障的运输。由于其 对自由基损伤敏感，视网膜必须具有保护性 机制。由于该组织与循环系统通过 屏障细胞层、保护性血浆蛋白不在此列 因此，可能含有过渡金属储存位点的组织 合成自己的保护性蛋白质。金属沉积部位 将使用细胞化学和扫描电子来确定视网膜 显微镜与色散X射线分析相结合。的控制 转铁蛋白、血红素结合蛋白和其他保护性蛋白的合成，例如 结合血红蛋白、金属硫蛋白和超氧化物的触珠蛋白 将在体内和体外研究消除自由基的歧化酶 在各种条件下使用 Northern 印迹和聚合酶链 反应检测信使 RNA 水平以及原位 杂交以检测合成位点。荧光技术 将用于确定是否存在过渡金属， 氧化应激和糖尿病会诱导体内自由基的产生 视网膜。上述视网膜病变的一个常见因素是血管生成， 常导致视网膜牵引。诱导机制 活性氧的毛细管生长可能涉及局部产生的 生长因子。视网膜中某些细胞产生的可能性 将研究氧化应激情况下的此类物质，并 鉴定所追求的生长因子。阐明角色 视网膜中的活性氧及其参与的方式 视网膜如何自我保护应表明这些保护机制如何 因视网膜病变而不堪重负。