reseatch for the neuro-protection ofretina and optic nerve by trans-corneal electrical stimulation

(1)。经角膜电刺激对视网膜和视神经的神经保护作用的分子机制。根据我们先前报道的经角膜电刺激通过上调胰岛素样生长因子1(IGF1)来阻止视网膜神经节细胞的神经元死亡，我们利用RT-PCR方法研究了电刺激培养的Mueller细胞是否上调了IGF-1的表达。结果表明，在停止电刺激30min后立即提取IGF-1mRNA，可显著增加IGF-1mRNA的表达。钙离子成像显示，细胞内钙离子浓度在电刺激开始后立即升高，在30min时达到1.5倍。应用L钙通道阻断剂硝苯地平可完全阻断钙离子浓度的升高。这些结果表明，电刺激促进胰岛素样生长因子-1基因的转录，这种现象与细胞内钙离子浓度通过L型钙通道升高有关。经角膜电刺激对视神经病变的临床研究我们观察了经角膜电刺激(TCES)对缺血性视神经病变(ION)和外伤性视神经病变(TON)眼的影响。对2003年6月至2006年5月在大阪大学附属医院接受TCES治疗的20例(20只眼)和10例(10只眼)色素沉着患者进行TCES检查，间隔6~8周。ION组6眼(30%)，TON组5眼(50%)，视力提高>0.3Log MAR单位。无一例视力下降超过0.3Log MAR单位。这些数据表明，TCES对某些离子和TON患者是有效的。

(1). Molecular mechanism of neroprotection for the retina and optic nerve by trans-corneal electrical stimulation.Based on our previous report that trans-corneal electrical stimulation to the retina prevented neuronal death of retinal ganglion cells with up-regulation of Insulin-like growth factor 1(IGF1), we studied if IGF-1 was up-regulated by electrical stimulation to the cultured Mueller cells using RT-PCR. The result was that the mRNA of IGF-1 significantly increased if the mRNA was extracted just after the cessation of 30 minutes electrical stimulation. The Ca++ imaging showed that intracellular Ca++ concentration increased just after the start of electrical stimulation, reached 1.5 fold at 30minutes. The increase of Ca++ concentration was completely blocked by the application of Nifedipine, an L-type Ca++ channel blocker. These results indicated that the electrical stimulation promotes the transcription of IGF-1 gene and this phenomenon is related to the increase of intracellular concentration of Ca++ through the L-type Ca++ channel.(2). Clinical investigation of trans-corneal electrical stimulation to the optic neuropathyWe investigated the effect of trans-corneal electrical stimulation (TcES) to the eye with ischemic optic neumpathy (ION) or traumatic optic neumpathy (TON). Consecutive chromic patients with ION (20 eyes) and TON (10 eyes) who visited Osaka University hospital between June 2003 and May 2006 in which TcES was applied with an interval of 6 to 8 weeks were examined. The increase of visual acuity greater than 0.3 Log MAR unit were observed in 6 eyes (30%) of ION and 5 eyes (50%) of TON. No patient decreased vision more than 0.3 Log MAR unit. These data suggests that TcES is effecive in some patients with ION and TON.