Jehle T, Meschede W, Dersch R, Feltgen N, Bach M, Lagrèze W A
Augenklinik des Klinikums der Albert-Ludwigs-Universität Freiburg i.Br., Killianstrasse 5, 79106, Freiburg i.Br.
Ophthalmologe. 2010 Apr;107(4):347-53. doi: 10.1007/s00347-009-2030-1.
The glycoprotein erythropoietin (EPO) has been shown to be protective in models of neuronal disease and reduced apoptosis of retinal ganglion cells (RGC) after transection of the optic nerve and in glaucoma. In this study we assessed in vivo the properties of EPO on survival of RGC after ischemia and optic nerve compression, as well as on postischemic visual function. Furthermore, the safety of intravitreal injection was assessed.
In all experiments, EPO was administered intravitreally in male Brown Norway rats. Ocular ischemia was induced by elevating the intraocular pressure for 55 min. The calibrated optic nerve compression was performed for 10 s. RGC were marked stereotactically and quantified by fluorescence microscopy. The retinal function was quantified by electroretinography (ERG) and the whole visual pathway by visual evoked potential (VEP).
EPO (2 and 20 units per eye, n=9-21) increased the survival of RGC after ischemia by 21+/-21% and 127+/-31% (mean +/- SEM) and after optic nerve compression by 28+/-12% and 58+/-13%. With EPO (20 units), postischemic function was increased, in ERG by 71+/-13% (a-wave) and 75+/-19% (b-wave) and in VEP by 264+/-65% (p=0.053). Neither the ERG parameters, nor the VEP, nor the number of RGC differed significantly after intravitreal injection of EPO (5, 50, and 200 units, n=6-7) in healthy eyes.
The combination of toxicological safety and protection of retinal neurons makes EPO a promising drug for ischemic retinal diseases and traumatic optic neuropathy.
糖蛋白促红细胞生成素(EPO)已被证明在神经元疾病模型中具有保护作用,并且在视神经横断后和青光眼模型中可减少视网膜神经节细胞(RGC)的凋亡。在本研究中,我们在体内评估了EPO对视神经缺血和受压后RGC存活的影响,以及对缺血后视觉功能的影响。此外,还评估了玻璃体内注射EPO的安全性。
在所有实验中,对雄性挪威棕色大鼠进行玻璃体内注射EPO。通过升高眼压55分钟诱导眼部缺血。进行校准的视神经压迫10秒。通过立体定位标记RGC,并通过荧光显微镜进行定量。通过视网膜电图(ERG)定量视网膜功能,通过视觉诱发电位(VEP)定量整个视觉通路。
EPO(每只眼2和20单位,n = 9 - 21)使缺血后RGC的存活率提高了21±21%和127±31%(平均值±标准误),视神经受压后提高了28±12%和58±13%。使用EPO(20单位)时,缺血后功能得到改善,ERG的a波增加了71±13%,b波增加了75±19%,VEP增加了264±65%(p = 0.053)。在健康眼中玻璃体内注射EPO(5、50和200单位,n = 6 - 7)后,ERG参数、VEP或RGC数量均无显著差异。
毒理学安全性和对视网膜神经元的保护作用相结合,使EPO成为治疗缺血性视网膜疾病和外伤性视神经病变的有前景的药物。