Miyara Nariko, Shinzato Manabu, Yamashiro Yoshito, Iwamatsu Akihiro, Kariya Ken-Ichi, Sawaguchi Shoichi
Department of Ophthalmology and Visual Sciences, School of Medicine, University of the Ryukyus, Okinawa, Japan.
Division of Cell Biology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan.
Jpn J Ophthalmol. 2008 Mar-Apr;52(2):84-90. doi: 10.1007/s10384-007-0507-5. Epub 2008 Apr 30.
To investigate global protein expression profiles in the retinas of normal and glucocorticoid-induced ocular hypertensive rats by proteomic analysis.
Ocular hypertension was induced by topical application of dexamethasone (DEX) for 4 weeks. Age-matched untreated rats served as controls. Intraocular pressure (IOP) was monitored by an electronic tonometer. Retinal protein expression profiling was carried out by two-dimensional fluorescence difference gel electrophoresis (2-D DIGE). Proteins were identified by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry.
In DEX-treated rats, average IOP was elevated significantly compared with controls. With DEX treatment, levels of four proteins were altered, as revealed by 2-D DIGE and MALDI-TOF mass spectrometry: apolipoprotein A1 (apoA1), a lipid-binding protein, upregulated 1.9-fold, P < 0.05; alpha A crystallin (CRYAA), a molecular chaperone, downregulated 2.7-fold, P < 0.01; superoxide dismutase 1 (SOD1), an antioxidant enzyme, downregulated 2.3-fold, P < 0.05; and triosephosphate isomerase 1 (TPI1), a glycolytic enzyme, downregulated 2.3-fold, P < 0.01.
Downregulation of CRYAA, SOD1, and TPI1, observed here after a short period of DEX-induced ocular hypertension, may be involved in the onset of neural damage in steroid-induced glaucoma.
通过蛋白质组学分析研究正常大鼠和糖皮质激素诱导的高眼压大鼠视网膜中的整体蛋白质表达谱。
通过局部应用地塞米松（DEX）4周诱导高眼压。年龄匹配的未治疗大鼠作为对照。用电子眼压计监测眼压。通过二维荧光差异凝胶电泳（2-D DIGE）进行视网膜蛋白质表达谱分析。通过基质辅助激光解吸电离飞行时间（MALDI-TOF）质谱鉴定蛋白质。
与对照组相比，DEX处理的大鼠平均眼压显著升高。通过2-D DIGE和MALDI-TOF质谱分析发现，DEX处理后四种蛋白质的水平发生了变化：载脂蛋白A1（apoA1），一种脂质结合蛋白，上调1.9倍，P<0.05；αA晶状体蛋白（CRYAA），一种分子伴侣，下调2.7倍，P<0.01；超氧化物歧化酶1（SOD1），一种抗氧化酶，下调2.3倍，P<0.05；磷酸丙糖异构酶1（TPI1），一种糖酵解酶，下调2.3倍，P<0.01。
在短期DEX诱导的高眼压后观察到的CRYAA、SOD1和TPI1的下调可能与类固醇诱导的青光眼神经损伤的发生有关。
