RETINAL DEGENERATION: A NEW ANIMAL MODEL

这些项目旨在深入了解病因， 遗传性视网膜变性（RD）的发病机制。 一种新的动物模型 将使用：罗得岛红鸡的突变株，其中 失明是通过常染色体隐性遗传方式传播的。 迄今为止， 发现新孵化的RD小鸡的ERG反应是不可测量的 而视网膜形态看起来类似于正常的小鸡视网膜， 接近同龄人的水平。 孵化后约1周， RD视网膜退化。 根据目前的资助，我们将描述发病机制，并确定 失明和感光细胞（PR）变性的病因， 模型 细胞死亡的时间和空间模式将通过 光学和电子显微镜。 孵化前的视网膜功能 通过ERG和瞳孔反射的测量来评估。 受累视网膜 将分析正常视色素的存在及其 回收利用以应对光。 将测定蛋白质和RNA合成 在正常和RD视网膜中，并进行比较。 PR细胞中的代谢过程 将研究这种非电视网膜：外节盘组件， 迁移、脱落、吞噬和降解将通过 放射自显影对标本中3 H-亮氨酸掺入的影响。 能力 视网膜神经节细胞合成和运输蛋白质将是 通过追踪3 H-脯氨酸的顺行运输和逆行运输来测量 辣根过氧化物酶的运输。 我们将决定在多大程度上 失明和PR退化可能是由全身性药物引起的， 方法：1将视杯移植于RD胚胎与正常胚胎之间， 早期和后期检查瞳孔反射、ERG和形态学; 通过在含有血清和正常人提取物的培养基中培养RD眼杯， 而正常眼杯在RD血清中培养， 浸提液-随后将检查形态学。 rd小鸡的大脑 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域。 最后，光在 将评估促进或延缓疾病。 通过探讨这些领域，我们希望阐明一些问题 与人类视网膜变性相关，有助于发现 代理人或操纵，可能有一天逮捕或防止这些 使人衰弱的疾病发生。

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.