FACTORS AFFECTING RETINAL SUSCEPTIBILITY TO DEGENERATION

影响视网膜退化易感性的因素

• 批准号: 3258977
• 负责人: LAURENCE M RAPP
• 金额: $ 9.06万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-03-01 至 1986-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3258977
• 关键词: aging; animal age group; antioxidants; catalase; disease /disorder model; disease /disorder prevention /control; disease /disorder proneness /risk; doxorubicin; drug adverse effect; electroretinography; environmental toxicology; glutathione peroxidase; histology; iron; light adverse effect; lipid peroxides; retina; retina degeneration; rod cell; superoxide dismutase; visual photoreceptor

The proposed study is an investigation of the regional susceptibility and age dependency of photoreceptor cells to degeneration. Photoreceptor-specific degeneration will be produced in rats by three procedures, namely: constant light exposure, intravitreal injection of ferrous sulfate, and intraperitoneal injection of adriamycin. Initial experimentation will delineate the time course of photoreceptor loss using light microscope and electroretinographic examination. Concomitantly, light microscopy will be utilized to determine the regional distribution of degeneration throughout the entire retina (i.e., inferior, superior, nasal and temporal quadrants). In subsequent experiments, the susceptibility to photoreceptor degeneration will be compared between different age-groups of rats ranging from pre-pubescent (4 - 5 weeks) to old (greater than 18 months). Preliminary results show that in rats, photoreceptor susceptibility to degeneration increases with age and is greater in the superior versus the inferior retina. One long term objective of this project is to conduct assays for certain enzymes and antioxidants in the retina which protect against photoreceptor degeneration, and to compare their activities between retinal regions and in different age groups of rats. The protective agents to be assayed will include superoxide dismutase, catalase, glutathione peroxidase and vitamin E. The premise that these biochemicals can protect against photoreceptor degeneration is based on accumulating evidence that the peroxidation of membrane lipids is directly involved in photoreceptor destruction. The hypothesis to be tested is that differences in the susceptibility to photoreceptor degeneration which occur between retinal regions and with age are due to the increased (or decreased) levels or activities of enzymes and antioxidants in the retina which protect against lipid peroxidation. To summarize, the aim of the proposed research is to investigate factors which influence the susceptibility of the retina to experimental photoreceptor degenerations. These experiments could provide a better understanding of the mechanisms which are involved in causing and protecting against photoreceptor degeneration. Furthermore, this information could be helpful in devising preventative measures against photoreceptor degenerations in humans which arise from certain drug treatments and exposure to environmental retinotoxins.

拟议的研究是一项区域敏感性调查， 光感受器细胞对退化的年龄依赖性。 光感受器特异性变性将在大鼠中产生的三个 程序，即：恒定曝光，玻璃体内注射 硫酸亚铁、阿霉素腹腔注射。 初始 实验将描绘感光细胞损失的时间过程， 光镜和视网膜电图检查。 同时， 光学显微镜将用于确定区域分布 整个视网膜的变性（即，下、上级、鼻 和时间象限）。 在随后的实验中，对 感光细胞退化将在不同年龄组之间进行比较， 从青春期前（4 - 5周）到老年（大于18岁）的大鼠 月）。 初步结果显示，在大鼠中， 对退化的敏感性随着年龄的增长而增加， 上级与下层视网膜。 长期目标之一 该项目是对某些酶和抗氧化剂进行分析， 视网膜，防止感光细胞变性，并比较 他们的活动之间的视网膜区域和不同年龄组的 大鼠 待测定的保护剂包括超氧化物 歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和维生素E。 前提 这些生化物质可以保护感光细胞不退化， 基于越来越多的证据表明，膜脂的过氧化作用是 直接参与感光细胞的破坏。 假设是 测试的是，感光细胞的敏感性差异， 视网膜区域之间随着年龄的增长而发生的变性是由于 酶的水平或活性增加（或降低）， 视网膜中的抗氧化剂，防止脂质过氧化。 到 总而言之，拟议研究的目的是调查 影响视网膜对实验感光细胞的敏感性 退化 这些实验可以更好地理解 参与引起和保护的机制 光感受器变性 此外，这些信息可能会有所帮助 在设计针对感光体退化的预防措施方面， 人类由于某些药物治疗和暴露于 环境视黄毒素