INHERITED RETINAL DEGENERATION

遗传性视网膜变性

• 批准号: 2163359
• 负责人: Sylvia B. Smith
• 金额: $ 10.18万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1997-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2163359
• 关键词: all trans retinol; disease /disorder model; electron microscopy; genetic disorder; high performance liquid chromatography; laboratory mouse; light microscopy; lipid biosynthesis; morphology; nutrition related tag; phagocytosis; phospholipids; pigmentation; posttranslational modifications; protein biosynthesis; retina degeneration; retinal pigment epithelium; retinaldehyde; retinitis pigmentosa; retinoid binding proteins; retinoids; rhodopsin; rod cell; spectrometry; thin layer chromatography; vesicle /vacuole; visual photoreceptor; vitiligo

The long range goal of this proposal is to determine the cause of the retinal degeneration in a newly described mouse model C57vit/vit. Photoreceptor cell nuclei are slowly lost over the course of a year in this animal model and the retinal pigment epithelium (RPE) is unevenly pigmented. The involvement of these two cell types and the protracted nature of the degeneration make the C57vit/vit a very promising model for human Retinitis Pigmentosa. Our preliminary data indicate that levels of the retinoids retinyl palmitate, 11-cis retinaldehyde and all-trans retinaldehyde are elevated at 6 weeks in the eyes of C57vit/vit mice; rhodopsin levels are significantly lower than controls by 12 weeks. In normal retinas, photoreceptors and RPE function cooperatively to regulate retinoids used in the visual cycle for the synthesis of rhodopsin. The proposed work will determine by HPLC whether the accumulation of retinoids is in photoreceptors or RPE. The functions of these two cell types will be evaluated to determine the site of the primary defect. Photoreceptor cell function will be assessed by morphometric studies of ROS turnover; spectrophotometric studies of rhodopsin levels; in vitro incubation studies of the synthesis and post-translational modifications of rhodopsin; and thin-layer chromatographic studies of phospholipid synthesis. RPE function will be assessed by morphometric analysis of the extent of pigmentation; and by determining the ability to phagocytize shed ROS discs by counting phagosomes in fixed retinal tissue obtained shortly after peak disc shedding. The morphological and biochemical data to be compiled from the proposed studies will guide development of intervention strategies and will serve as a yardstick against which their efficacy can be evaluated.

该提议的远距离目标是确定 新描述的小鼠模型C57VIT/VIT中的视网膜变性。 一年中，感光细胞细胞核在一年中慢慢丢失 该动物模型和视网膜色素上皮（RPE）不均匀 色素。 这两种细胞类型的参与和持久的 退化的性质使C57VIT/VIT成为非常有前途的模型 人视网膜炎色素。 我们的初步数据表明 视网膜类视网膜棕榈酸酯，11-cis视网膜甲醛和全型 在C57VIT/VIT小鼠眼中，视网膜醛在6周时升高； 在12周之前，视紫红质水平明显低于对照。 在 正常的视网膜，感光器和RPE合作起作用以调节 视视周期中用于合成视紫红质的视网膜类似。 这 建议的工作将通过HPLC确定是否积累 视网膜类动物在感光器或RPE中。 这两个单元的功能 将评估类型以确定主要缺陷的部位。 光感受器细胞功能将通过形态计量学评估 ROS失误；视紫红质水平的分光光度法研究；体外 对合成和翻译后修饰的孵育研究 Rhodopsin;和磷脂的薄层色谱研究 合成。 RPE功能将通过形态计量分析评估 色素沉着的程度；并确定吞噬能力的能力 通过在获得的固定视网膜组织中计数吞噬体来分支ROS椎间盘 峰值脱落后不久。 形态学和生化数据 根据拟议的研究汇编将指导开发 干预策略，并将作为其码数 可以评估功效。