RETINAL DEGENERATION: A NEW ANIMAL MODEL

这些项目旨在提供对病因和 遗传性视网膜变性的发病机制。一种新的动物模型 将被利用：一种罗德岛红鸡的突变株，其中 失明是通过常染色体隐性遗传方式传播的。到目前为止，我们有 发现新孵化的RD雏鸡的ERG反应是不可测量的 而视网膜的形态看起来类似于正常的小鸡视网膜，其ERG 接近成年人在同一年龄的水平。在孵化后大约1周后， 视网膜变性。 在目前的拨款下，我们将描述发病机制并确定 失明和光感受器细胞变性的病因 模特。细胞死亡的时间和空间模式将通过 光学显微镜和电子显微镜。孵化前的视网膜功能 通过视网膜电流图和测量瞳孔反射进行评估。受影响的视网膜 将被分析是否存在正常的视觉色素及其 对光作出反应的循环利用。蛋白质和RNA的合成将被检测 并对正常视网膜和视网膜脱离视网膜进行比较。PR细胞在体内的代谢过程 这种非电视网膜将被研究：外节段视盘组件， 迁移、脱落、吞噬和降解将通过 放射自显影技术在标本中掺入~3H-亮氨酸。具备以下能力 视网膜神经节细胞合成和运输蛋白质将 示踪法测定~3H-脯氨酸的顺行转运和逆行转运 辣根过氧化物酶的运输。我们将确定在多大程度上 失明和PR退化可能是由2%的全身因素引起的 方法：1将视网膜脱离胚胎与正常胚胎进行视杯移植。 早期和后期检测瞳孔反射、视网膜电图和形态学； 在含有正常人血清和提取物的培养液中培养RD眼针 将正常眼球的雏鸡培养在RD血清和 萃取物--随后将检查其形态。RD雏鸡的大脑 将检查视觉中心组织学的正常性以及 视网膜神经节细胞的靶区。最后，光在其中的作用 将对促进或延缓疾病进行评估。 通过对这些领域的探讨，我们希望澄清一些问题 与人类视网膜退行性变有关并有助于发现 有一天可能会逮捕或阻止这些人的代理人或操纵 使人衰弱的疾病不会发生。

These projects are designed to provide insight into the etiology and pathogenesis of hereditary retinal degeneration (rd). A new animal model will be utilized: a mutant strain of Rhode Island Red chickens in which blindness is transmitted by an autosomal recessive mode. To date we have found that the ERG response of newly hatched rd chicks is not measurable while retinal morphology appears similar to a normal chick retina whose ERG is near adult levels at the same age. After about 1 week post-hatching, the rd retinas degenerate. Under the present grant we will describe the pathogenesis and determine the etiology of blindness and photoreceptor (PR) cell degeneration in this model. The temporal and spatial patterns of cell death will be analyzed by light and electron microscopy. Retinal function prior to hatching will be assessed by ERG and measurement of the pupillary reflex. Affected retinas will be analyzed for the presence of normal visual pigments and their recycling in response to light. Protein and RNA synthesis will be assayed in normal and rd retinas and compared. Metabolic processes in PR cells in this non-electrical retina will be studied: outer segment disc assembly, migration, shedding, phagocytosis and degradation will be tested by autoradiography on incorporation of 3H-leucine in specimens. Ability of retinal ganglion cells to synthesize and transport proteins will be measured by tracing anterograde transport of 3H-proline and the retrograde transport of horseradish peroxidase. We will determine to what extent blindness and PR degeneration might be caused by systemic agents by 2 methods: 1 by grafting optic cups between rd and normal embryos at an early stage and later testing pupillary reflex, ERG and morphology; and 2 by culturing rd eyecups in media containing serum and extracts from normal chicks while normal eyecups are cultured in rd serum and extracts--subsequently morphology will be examined. Brains of rd chicks will be examined for normalcy of visual center histology as well as for target areas of retinal ganglion cells. Finally, the role of light in promoting or retarding the disease will be assessed. By probing these areas, we hope to elucidate some of the questions associated with human retinal degenerations and contribute to finding agents or manipulations that may some day arrest or prevent these debilitating diseases from occurring.