Study of theretinal ganglion cell specific gene, optic atrophy, and gene threrapy

视网膜神经节细胞特异性基因、视神经萎缩及基因治疗的研究

基本信息

批准号：
12470368
负责人：
MASHIMA Yukihiko
金额：
$ 9.92万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470368/
关键词：
retinal ganglion cell promotor mause amine oxidase Leber's disease idebenone human amine oxidase ベクター

项目摘要

Mouse homologue of AOC2 was cloned for haracterization. Real-time quantitative PCR and in situ hybridization were performed to determine specific expression of AOC2 in mouse retina, especially in retinal ganglion cells. The copper-binding motif and the enzyme active site of AOC1 and AOC3 were both preserved in mouse AOC2 protein. Mouse AOC2 gene was located 1,526 bp downstream of Psme3 gene for PA-28 gamma-subunit and 775 bp upstream of AOC3 gene. We have plan to construct the vector that can particularly transport some gene into ganglion cells.Visual recovery and its characteristics were investigated in patients with Leber's hereditary optic neuropathy (LHON) developed in teens. Fourteen patients who had the 11778 mutation were included in this study. The averaged age of onset of the disease was 14.8 years. Six of 14 patients were treated with idebenone and vitamins B2 and C. Seven of the 14 LHON patients (11 of 28 eyes) showed a visual recovery between 0.3 and 1.0, and fenestrated central scotomas by the Humphrey 10-2 threshold. Five of the 7 patients were treated with medicines. The nasal side of the central visual fields showed a greater sensitivity than the temporal side in 10 of the 11 eyes. Nerve fiber bundles other than the papillomacular bundles may have a greater potential to recover function in patients with LHON.

克隆 AOC2 的小鼠同源物以进行表征。采用实时定量PCR和原位杂交测定AOC2在小鼠视网膜，特别是视网膜神经节细胞中的特异性表达。小鼠AOC2蛋白中均保留了AOC1和AOC3的铜结合基序和酶活性位点。小鼠 AOC2 基因位于 PA-28 γ 亚基 Psme3 基因下游 1,526 bp 处，位于 AOC3 基因上游 775 bp 处。我们计划构建能够专门将某些基因转运到神经节细胞中的载体。对青少年时期患有莱伯氏遗传性视神经病变（LHON）的患者进行了视力恢复及其特征的研究。本研究纳入了 14 名携带 11778 突变的患者。该病的平均发病年龄为14.8岁。 14 名患者中的 6 名接受了艾地苯醌以及维生素 B2 和 C 治疗。14 名 LHON 患者中的 7 名（28 只眼中的 11 只）显示视力恢复在 0.3 至 1.0 之间，并且中央暗点出现 Humphrey 10-2 阈值。 7名患者中有5名接受了药物治疗。 11 只眼睛中，有 10 只眼睛的中央视野的鼻侧表现出比颞侧更高的敏感性。 LHON 患者中除乳头黄斑束以外的神经纤维束可能具有更大的恢复功能的潜力。