MODELS OF PHOTORECEPTOR DISEASE

光感受器疾病模型

• 批准号: 6195713
• 负责人: TIANSEN LI
• 金额: $ 30.1万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-01-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6195713
• 关键词: confocal scanning microscopy; disease /disorder model; electron microscopy; electrophysiology; electroretinography; enzyme linked immunosorbent assay; gene expression; gene mutation; genetically modified animals; guanosinetriphosphatases; histogenesis; immunoprecipitation; laboratory mouse; light microscopy; polymerase chain reaction; protein protein interaction; protein structure function; retina degeneration; retinitis pigmentosa; rhodopsin; rod cell; visual photoreceptor; visual phototransduction; western blottings

DESCRIPTION (Adapted from applicant's abstract): The main objective of this proposal is to analyze the functions of three genes that have been shown or to have been proposed as causes of retinal degenerative diseases. Preliminary studies indicate that products of these genes are not directly involved in phototransduction but may participate in the membrane/protein trafficking that are the basis of photoreceptor outer segment renewal, an essential but poorly understood process in photoreceptor cell biology. Specific hypotheses have been put forward regarding the physiological functions of each of these proteins, linking them to membrane vesicle budding, specificity of vesicle translocation, or an active transport function across the connecting cilium, respectively. A deficit in any of these functions should severely impact photoreceptor function and viability, and therefore will be a cause of retinal degeneration. Experimental approaches will be emphasize on a combination of in vivo analyses of animal models, in vitro biochemical characterizations, and a dissection of the molecular pathways through a search for interacting proteins. These studies are likely to generate new insight into the process of photoreceptor membrane renewal at the molecular level. It is our view that following the elucidation of the phototransduction cascade, many of the remaining genes which are involved in retinal degeneration but are not yet understood, may encode essential functions in the process of photoreceptor membrane renewal. Therefore the proposed studies should be of major importance to photoreceptor disease.

描述（改编自申请人摘要）：本文的主要目标 一项建议是分析三个已被证明的基因的功能， 已经被认为是视网膜变性疾病的原因。初步 研究表明，这些基因的产物并不直接参与 光转导，但可能参与膜/蛋白质运输， 是光感受器外节更新的基础，这是一个必要的，但很差的 光感受器细胞生物学的理解过程。具体的假设是 提出了关于这些蛋白质中每一种的生理功能， 将它们与膜囊泡出芽，囊泡移位的特异性， 或跨连接纤毛的主动运输功能。一 这些功能中的任何一个的缺陷都将严重影响感光器功能 和活力，因此将是视网膜变性的原因。 实验方法将强调结合体内分析 动物模型，体外生化表征，以及解剖 通过寻找相互作用的蛋白质的分子途径。这些研究 可能会对感光膜的过程产生新的见解 在分子水平上的更新。我们认为，在作出澄清后， 在光传导级联反应中，许多剩下的基因， 参与视网膜变性，但尚未了解，可能编码 在光感受器膜更新过程中的重要功能。因此 所提出的研究对于光感受器疾病应该是非常重要的。