Kimura Atsuko, Namekata Kazuhiko, Guo Xiaoli, Harada Chikako, Harada Takayuki
Visual Research Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
Int J Mol Sci. 2016 Sep 20;17(9):1584. doi: 10.3390/ijms17091584.
Neurotrophic factors play key roles in the development and survival of neurons. The potent neuroprotective effects of neurotrophic factors, including brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), glial cell-line derived neurotrophic factor (GDNF) and nerve growth factor (NGF), suggest that they are good therapeutic candidates for neurodegenerative diseases. Glaucoma is a neurodegenerative disease of the eye that causes irreversible blindness. It is characterized by damage to the optic nerve, usually due to high intraocular pressure (IOP), and progressive degeneration of retinal neurons called retinal ganglion cells (RGCs). Current therapy for glaucoma focuses on reduction of IOP, but neuroprotection may also be beneficial. BDNF is a powerful neuroprotective agent especially for RGCs. Exogenous application of BDNF to the retina and increased BDNF expression in retinal neurons using viral vector systems are both effective in protecting RGCs from damage. Furthermore, induction of BDNF expression by agents such as valproic acid has also been beneficial in promoting RGC survival. In this review, we discuss the therapeutic potential of neurotrophic factors in retinal diseases and focus on the differential roles of glial and neuronal TrkB in neuroprotection. We also discuss the role of neurotrophic factors in neuroregeneration.
神经营养因子在神经元的发育和存活中发挥着关键作用。神经营养因子具有强大的神经保护作用,包括脑源性神经营养因子(BDNF)、睫状神经营养因子(CNTF)、胶质细胞源性神经营养因子(GDNF)和神经生长因子(NGF),这表明它们是神经退行性疾病的良好治疗候选物。青光眼是一种导致不可逆失明的眼部神经退行性疾病。其特征是视神经受损,通常是由于高眼压(IOP)以及称为视网膜神经节细胞(RGCs)的视网膜神经元的进行性退化。目前青光眼的治疗重点是降低眼压,但神经保护也可能有益。BDNF是一种强大的神经保护剂,尤其对RGCs有效。将BDNF外源性应用于视网膜以及使用病毒载体系统增加视网膜神经元中BDNF的表达,在保护RGCs免受损伤方面均有效。此外,丙戊酸等药物诱导BDNF表达也有利于促进RGCs的存活。在本综述中,我们讨论了神经营养因子在视网膜疾病中的治疗潜力,并重点关注胶质细胞和神经元TrkB在神经保护中的不同作用。我们还讨论了神经营养因子在神经再生中的作用。