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保护的分子机制。基于我们之前的报道，经角膜电刺激视网膜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，我们使用RT-PCR研究了电刺激培养的Mueller细胞是否上调IGF-1。结果表明，如果在电刺激结束30分钟后立即提取IGF-1 mRNA，则IGF-1 mRNA显著升高。钙离子成像显示，电刺激刚开始时细胞内钙离子浓度升高，30min时达到1.5倍。l型Ca++通道阻滞剂硝苯地平完全阻断了Ca++浓度的增加。这些结果表明，电刺激促进了IGF-1基因的转录，这一现象与通过l型ca2 +通道使细胞内ca2 +浓度升高有关(2)。经角膜电刺激对视神经病变的临床研究我们研究了经角膜电刺激对缺血性视神经病变（ION）和外伤性视神经病变（TON）的影响。对2003年6月至2006年5月期间到大阪大学医院就诊的连续慢性ION（20只眼）和TON（10只眼）患者进行了检查，这些患者每隔6至8周使用TcES。ION组6眼（30%）、TON组5眼（50%）视力增加大于0.3 Log MAR单位。没有患者视力下降超过0.3 Log MAR单位。这些数据表明，TcES对部分ION和TON患者有效。

(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.