FACTORS AFFECTING RETINAL SUSCEPTIBILITY TO DEGENERATION

拟议的研究是对区域易感性和 光感受器细胞退变的年龄依赖性。 光感受器特异性退行性变将在大鼠中产生 程序，即：恒定光照，玻璃体内注射 硫酸亚铁和阿霉素腹腔注射。首字母 实验将描绘光感受器丢失的时间进程 光镜和视网膜电流图检查。伴随而来的是， 光学显微镜将被用来确定 整个视网膜的变性(即，下、上、鼻 和时间象限)。在随后的实验中，易感性 感光细胞退行性变将在不同年龄段之间进行比较- 大鼠从青春期前(4-5周)到老年(大于18周)不等 月)。初步结果显示，在大鼠体内，光感受器 退行性变的易感性随着年龄的增长而增加，在 上视网膜对下视网膜。这样做的一个长期目标 该项目是对人体内某些酶和抗氧化剂进行检测。 防止光感受器退化的视网膜，并比较 视网膜区域之间和不同年龄组之间的活动 老鼠。被检测的保护剂将包括超氧化物 歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和维生素E 这些生物化学物质可以防止光感受器退化 基于越来越多的证据表明，膜脂过氧化是 直接参与光感受器的破坏。假设是 测试的是感光器对光敏感度的差异 发生在视网膜区域之间并随年龄增长的退化是由于 酶和酶活性的增加(或降低) 视网膜中的抗氧化剂，可防止脂质过氧化。至 总而言之，拟议研究的目的是调查以下因素 影响视网膜对实验性光感受器的敏感性 堕落的人。这些实验可以让我们更好地理解 引起和预防疾病的机制 光感受器退化。此外，这些信息可能会有所帮助 在制定预防光感受器退化的措施方面 由于某些药物治疗和暴露于 环境维甲酸毒素。

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.