Nakazawa Toru, Takahashi Hidetoshi, Shimura Masahiko
Department of Ophthalmology and Visual Science, Tohoku University Graduate School of Medicine, Sendai, 980-8574 Miyagi, Japan.
Brain Res. 2006 Jun 6;1093(1):141-9. doi: 10.1016/j.brainres.2006.03.084. Epub 2006 May 11.
The neuroprotective effects of estrogen on neuronal cells in central nervous system have been described previously, however, the mechanisms of neuroprotective effect of estrogen against retinal ganglion cell (RGC) death has not been well identified. To examine the role of endogenous sex steroids produced in ovary, retina samples were prepared from female rats with or without ovariectomy and the density of RGC was calculated. Ovariectomy alone had no effect on the density of fluorogold (FG)-labeled RGC without injury, while the density of surviving RGC after optic nerve axotomy with ovariectomy was significantly decreased compared to that without ovariectomy. To examine the role of exogenous sex steroids, 17beta-estradiol was injected into the vitreous cavity in ovariectomized rats and showed neuroprotective effect on axotomy-induced RGC death while exogenous progesterone showed no effect. Immunoblot and immunohistochemical analysis demonstrated that ERK-c-Fos signal transduction pathway was activated by exogenous 17beta-estradiol in ganglion cell layer. U0126, an ERK inhibitor, inhibited the neuroprotective effect of estrogen on axotomized RGC death. These data suggest that estrogen has neuroprotective effect through activation of ERK-c-Fos signaling pathway on axotomy-induced RGC death. The neuroprotective effect of estrogen may have therapeutic benefits in retinal diseases associated with RGC death such as glaucoma.
雌激素对中枢神经系统神经元细胞的神经保护作用此前已有描述，然而，雌激素对视网膜神经节细胞（RGC）死亡的神经保护作用机制尚未完全明确。为了研究卵巢产生的内源性性激素的作用，制备了去卵巢和未去卵巢雌性大鼠的视网膜样本，并计算了RGC的密度。单独去卵巢对未受伤的荧光金（FG）标记的RGC密度没有影响，而与未去卵巢的大鼠相比，去卵巢大鼠视神经切断术后存活的RGC密度显著降低。为了研究外源性性激素的作用，将17β-雌二醇注入去卵巢大鼠的玻璃体腔，结果显示其对切断诱导的RGC死亡具有神经保护作用，而外源性孕酮则无此作用。免疫印迹和免疫组织化学分析表明，外源性17β-雌二醇在神经节细胞层激活了ERK-c-Fos信号转导通路。ERK抑制剂U0126抑制了雌激素对切断诱导的RGC死亡的神经保护作用。这些数据表明，雌激素通过激活ERK-c-Fos信号通路对切断诱导的RGC死亡具有神经保护作用。雌激素的神经保护作用可能对与RGC死亡相关的视网膜疾病如青光眼具有治疗益处。
