RETINAL DEGENERATION: A NEW ANIMAL MODEL

人类遗传性视网膜变性知之甚少 开始于生命早期、中期或晚期， 导致完全失明。 像视网膜炎和年龄这样的并发症- 相关性黄斑病变是这类疾病中最常见的 疾病。 本文提出用实验来阐明一个人失明的原因。 人类疾病的动物模型。 这个模型，rd，或者 鸡视网膜退化株，表现出隐性模式， 一种导致早期失明的缺陷的遗传传播 生活 病变开始于后眼底的一个位点， 周边，有伴随的色素变化和视觉 细胞在电生理测试显示它们有缺陷后死亡。 因此，该模型可用作研究人类的替代物。 综合征 初步研究表明，rd中导致失明的缺陷 小鸡是在视觉转导水平：转换的 光能转化为电脉冲。 目前拟议的研究 格兰特的目的是检查几个过程中涉及的视觉 转导 氧化代谢与视色素漂白 用硝基四氮唑蓝组织化学法 反应和早期受体电位。 存在 或缺乏特定的视网膜蛋白（如视色素 蛋白和G蛋白，将通过免疫细胞化学进行检查 和蛋白质分离技术。 我们将确定视紫红质 在对光的反应中被磷酸化， 突变体中的核苷酸水平与正常视力的核苷酸水平 小妞们 视蛋白合成和外节更新将是 进行了生化和解剖学的检测 最后，Na-K- ATP酶分子，控制重要的膜离子 将分析光感受器中的泵，作为可能的 失明的原因/影响。 这些实验将使我们深入了解失明的原因 并进入正常的视觉传导过程。

Human hereditary retinal degenerations are poorly understood diseases that begin in early, middle or late life and frequently procede to total blindness. Syndromes such as retinitis and age- related maculopathy are the most common disorders in the class of diseases. Experiments are proposed to elucidate the cause of blindness in an animal model for the human diseases. This model, the rd, or retinal degenerate strain of chickens, exhibits a recessive mode of genetic transmission of a defect that leads to blindness early in life. The lesion begins as a locus in the posterior fundus, spreads peripherally, has accompanying pigmentary changes and the visual cells die after electrophysiological tests show them defective. Therefore, this model is useful as a surrogate for studying human syndromes. Preliminary studies suggest that the defect causing blindness in rd chicks is at the level of visual transduction: the conversion of light energy to electrical impulse. Studies proposed in the current grant are aimed at examining several processes involved in visual transduction. Oxidative metabolism and visual pigment bleaching will be examined by the nitroblue tetrazolium histochemical reaction and the early receptor potential, respectively. Presence or absence of specific retinal proteins (such as visual pigment proteins and G-protein, will be examined by immunocytochemistry and protein separation techniques. We will determine if rhodopsin is phosphorylated in response to light and compare cylic nucleotide levels in the mutants to those in normally sighted chicks. Opsin synthesis and outersegment renewal will be examined biochemically and anatomically. Finally, the Na-K- ATPase molecule, which controls an important membrane ion pump in photoreceptors will be analyzed, as a possible cause/effect of the blindness. These experiments will provide insight into the cause of blindness and into the normal processes of visual transduction.