PHOTORECEPTOR RETINOL DEHYDROGENASES AND VISION

光感受器视黄醇脱氢酶与视力

• 批准号: 8168350
• 负责人: Anne Kasus-Jacobi
• 金额: $ 10.95万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168350
• 关键词: Aldehydes; Blindness; Cell Death; Computer Retrieval of Information on Scientific Projects Database; Drug Metabolic Detoxication; Enzymes; Funding; Genes; Grant; Human; Institution; Leber' s amaurosis; Lipid Peroxidation; Molecular; Mutation; Oxidoreductase; Patients; Photoreceptors; Research; Research Personnel; Resources; Retinol dehydrogenase; Role; Source; United States National Institutes of Health; Vision; early onset; inherited retinal degeneration; interest

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Retinol Dehydrogenases RDH11 and RDH12 are closely related microsomal oxidoreductases located in photoreceptor inner segments. Mutations in the human RDH12 gene induce the most severe and early onset type of inherited retinal degeneration, called Leber Congenital Amaurosis Type 3 (LCA3). We are investigating the function of this enzyme and the molecular mechanisms leading to vision loss and photoreceptor cell death in RDH12-induced LCA. We are specifically interested by the detoxification role of RDH12, and of other retinol dehydrogenases such as RDH11, RDH13, and DHRS3, all located in photoreceptor cells, in different subcellular compartments. We have recently discovered that RDH12 can detoxify damaging aldehydes produced by lipid peroxidation in photoreceptor cells. Such endogenous protection might be necessary to maintain the functional integrity of photoreceptor cells. This hypothesis predicts that photoreceptors die in LCA3 patients due to an absence of this detoxification activity.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 视黄醇脱氢酶RDH11和RDH12是位于光感受器内段的两个密切相关的微粒体氧化还原酶。人类RDH12基因突变会导致最严重和最早发病的遗传性视网膜变性，称为Leber先天性黑色素沉着症3型(LCA3)。我们正在研究这种酶的功能以及在RDH12诱导的LCA中导致视力丧失和光感受器细胞死亡的分子机制。我们特别感兴趣的是RDH12的解毒作用，以及其他视黄醇脱氢酶，如RDH11、RDH13和DHRS3，它们都位于不同的亚细胞室的感光细胞中。我们最近发现RDH12可以解毒光感受器细胞中由脂质过氧化产生的破坏性醛。这种内源性保护可能是维持光感受器细胞功能完整性所必需的。这一假说预测，由于LCA3患者缺乏这种解毒活性，光感受器会死亡。