The Research for Elucidation of Molecular Mechanism of Glaucomatous Optic Neuropathy and Development of Efficacious Treatment

青光眼性视神经病变分子机制的阐明及有效治疗方法的开发

• 批准号: 17390466
• 负责人: ABE Haruki
• 金额: $ 10.05万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390466/
• 关键词: Glaucoma; Optic Nerve Head; DNA Microarray; Retinal Ganglion Cell Death; Mitochondria; 実験緑内障眼; 免疫組織化学; リアルタイムRT-PCR

Visco-elastic solution Healon-V* was intra-camerally injected in the unilateral eye of two cynomolgus monkeys, and experimental acute glaucoma model eyes were produced. The intraocular pressure (IOP) was measured by Parkins' applanation tonometer, and the IOP of the two glaucomatous eyes were confirmed to be sustained over 30mmHg, while those of contralateral control eyes were under 15mmHg. After the IOP elevation of 3 days, the monkeys were painlessly sacrificed, and the glaucomatous and control eyes were enucleated including retrobulbar optic nerve. The lamina cribrosa tissue including pre-laminar and post-laminar portion were excised under binocular microscope, and the total RNA was extracted and purified. DNA microarray, Human Genome U133 2.0 Array, Affimetrix (Oligo-array, single color, approximately 39,000 transcriptional products) were utilized to detect up/down regulated RNA after IOP elevation, and the data was analyzed with Atlas-Image 2.01. Ninety up-regulated genes were selected under the condition of "detection : present-present" and "signal log ratio > 2.0", and 62 down-regulated genes were selected under the condition of "signal log ratio <-2.0". Up-regulated genes included cytoskeleton (profilin 1, thrombospondin 2, protocadherin 8, CD44 antigen, BMP-2), signal transduction (G protein), extracellular matrix (collagen types IV, VI, XV), immune response (guanylate binding protein 2), transcription factor (v-fos, junB), transport (ceruloplasmin), TIMP-1, etc. Down-regulated genes included cytoskeleton (oligodendrocyte myelin glycoprotein), immune response (myelin basic protein), transcription factor (oligodendrocyte transcription factor 1), TGF-2, etc. Meanwhile, there was no significant increase or decrease in the gene expression related to tissue remodeling in the acute phase of IOP elevation.

将粘弹剂Healon-V* 注射于两只食蟹猴的单侧眼内，制备实验性急性青光眼模型眼。用Parkins压平眼压计测量眼压，证实患眼眼压均在30 mmHg以上，对侧对照眼眼压均在15 mmHg以下。在IOP升高3天后，无痛处死猴，摘除包括球后视神经在内的青光眼和对照眼。在双目显微镜下切除筛板组织，包括筛板前和筛板后部分，提取并纯化总RNA。利用DNA微阵列、Human Genome U133 2.0 Array、Affibrium（Oligo-array，单色，约39，000个转录产物）检测IOP升高后上调/下调的RNA，并使用Mifas-Image 2.01分析数据。在“检测：存在-存在”和“信号对数比> 2.0”的条件下筛选出90个上调基因，在“信号对数比<-2.0”的条件下筛选出62个下调基因。上调表达的基因包括细胞骨架（profilin 1，thrombospondin 2，protocadherin 8，CD 44 antigen，BMP-2），信号转导（G蛋白），细胞外基质（IV、VI、XV型胶原蛋白），免疫反应鸟苷酸结合蛋白2，转录因子（v-fos，junB），运输下调表达的基因包括细胞骨架蛋白（cytoskeleton，cytoskeleton（少突胶质细胞髓鞘糖蛋白），免疫应答（髓鞘碱性蛋白），转录因子（少突胶质细胞转录因子1）、TGF-2等。同时，在IOP升高的急性期，与组织重塑相关的基因表达没有显著增加或减少。

项目成果

Guidelines for Glaucoma Second edition

青光眼指南第二版

• 发表时间: 2006
• 期刊: J Jpn Ophthalmol Soc 110(10)
• 作者: Yasuaki Harabuchi;et.al;原渕保明;Takeo Fukuchi;Takeo Fukuchi;Haruki Abe;Haruki Abe;澤田 英子;阿部春樹;白柏 基宏;福地 健郎;Fumie Hayama;Takeo Fukuchi;Motohiro Shirakashi;Takeo Fukuchi;Hideko Sawada;Haruki Abe
• 通讯作者: Haruki Abe

緑内障の視神経乳頭形状解析

青光眼的视盘形状分析

• 发表时间: 2005
• 期刊: 神経眼科 22・2
• 作者: Yasuaki Harabuchi;et.al;原渕保明;Takeo Fukuchi;Takeo Fukuchi;Haruki Abe;Haruki Abe;澤田 英子;阿部春樹;白柏 基宏;福地 健郎;Fumie Hayama;Takeo Fukuchi;Motohiro Shirakashi;Takeo Fukuchi;Hideko Sawada;Haruki Abe;Haruki Abe;Haruki Abe;Haruki Abe;阿部春樹;阿部春樹;白柏 基宏;澤田 英子;Tetsuya Togano;Takeo Fukuchi;Masaaki Seki;Kiyoshi Yaoeda;Motohiro Shirakashi;Takeo Fukuchi;K.Hashimoto;Haruki Abe;Masaaki Seki;福地 健郎;阿部 春樹;阿部 春樹;白柏 基宏
• 通讯作者: 白柏 基宏

GDx VCCの原理と臨床応用

GDx VCC原理及临床应用

• 发表时间: 2005
• 期刊: 臨床眼科 59・11
• 作者: Yasuaki Harabuchi;et.al;原渕保明;Takeo Fukuchi;Takeo Fukuchi;Haruki Abe;Haruki Abe;澤田 英子;阿部春樹;白柏 基宏;福地 健郎;Fumie Hayama;Takeo Fukuchi;Motohiro Shirakashi;Takeo Fukuchi;Hideko Sawada;Haruki Abe;Haruki Abe;Haruki Abe;Haruki Abe;阿部春樹;阿部春樹;白柏 基宏;澤田 英子;Tetsuya Togano;Takeo Fukuchi;Masaaki Seki;Kiyoshi Yaoeda;Motohiro Shirakashi;Takeo Fukuchi;K.Hashimoto;Haruki Abe;Masaaki Seki;福地 健郎;阿部 春樹;阿部 春樹;白柏 基宏;原 浩昭;白柏 基宏;上田 潤;上田 潤;福地 健郎;福島 淳志;白柏 基宏
• 通讯作者: 白柏 基宏

Intraocular Pressure in Neovascular Glaucoma Patients with Latanoprost.

拉坦前列素治疗新生血管性青光眼患者的眼压。

• 发表时间: 2005
• 期刊: Journal of the eye 22(11)
• 作者: Yasuaki Harabuchi;et.al;原渕保明;Takeo Fukuchi;Takeo Fukuchi;Haruki Abe;Haruki Abe;澤田 英子;阿部春樹;白柏 基宏;福地 健郎;Fumie Hayama;Takeo Fukuchi;Motohiro Shirakashi;Takeo Fukuchi;Hideko Sawada;Haruki Abe;Haruki Abe;Haruki Abe;Haruki Abe;阿部春樹;阿部春樹;白柏 基宏;澤田 英子;Tetsuya Togano;Takeo Fukuchi;Masaaki Seki;Kiyoshi Yaoeda;Motohiro Shirakashi;Takeo Fukuchi;K.Hashimoto;Haruki Abe;Masaaki Seki;福地 健郎;阿部 春樹;阿部 春樹;白柏 基宏;原 浩昭;白柏 基宏;上田 潤;上田 潤;福地 健郎;福島 淳志;白柏 基宏;葉山 文恵;福地 健郎;八百枝 潔;Tetsuya Togano;Takeo Fukuchi;Masaaki Seki;Kiyoshi Yaoeda;Motohiro Shirakashi;Takeo Fukuchi;Kaoru Hashimoto;Masaaki Seki;Haruki Abe;Haruki Abe;Motohiro Shirakashi;Hiroaki Hara;Atsushi Fukushima;Haruki Abe;Takeo Fukuchi
• 通讯作者: Takeo Fukuchi

Distinction of the Japan Glaucoma Society Guidelines for Glaucoma.

日本青光眼协会青光眼指南的区别。

• 发表时间: 2005
• 期刊: Journal of the eye 22
• 作者: Yasuaki Harabuchi;et.al;原渕保明;Takeo Fukuchi;Takeo Fukuchi;Haruki Abe;Haruki Abe;澤田 英子;阿部春樹;白柏 基宏;福地 健郎;Fumie Hayama;Takeo Fukuchi;Motohiro Shirakashi;Takeo Fukuchi;Hideko Sawada;Haruki Abe;Haruki Abe;Haruki Abe;Haruki Abe;阿部春樹;阿部春樹;白柏 基宏;澤田 英子;Tetsuya Togano;Takeo Fukuchi;Masaaki Seki;Kiyoshi Yaoeda;Motohiro Shirakashi;Takeo Fukuchi;K.Hashimoto;Haruki Abe;Masaaki Seki;福地 健郎;阿部 春樹;阿部 春樹;白柏 基宏;原 浩昭;白柏 基宏;上田 潤;上田 潤;福地 健郎;福島 淳志;白柏 基宏;葉山 文恵;福地 健郎;八百枝 潔;Tetsuya Togano;Takeo Fukuchi;Masaaki Seki;Kiyoshi Yaoeda;Motohiro Shirakashi;Takeo Fukuchi;Kaoru Hashimoto;Masaaki Seki;Haruki Abe;Haruki Abe;Motohiro Shirakashi;Hiroaki Hara;Atsushi Fukushima;Haruki Abe;Takeo Fukuchi;Takeo Fukuchi;Haruki Abe
• 通讯作者: Haruki Abe