COMBINED EFFECT OF BRAIN-DERIVED NEUROTROPHIC FACTOR AND LINGO-1 FUSION PROTEIN ON LONG-TERM SURVIVAL OF RETINAL GANGLION CELLS IN CHRONIC GLAUCOMA
COMBINED EFFECT OF BRAIN-DERIVED NEUROTROPHIC FACTOR AND LINGO-1 FUSION PROTEIN ON LONG-TERM SURVIVAL OF RETINAL GANGLION CELLS IN CHRONIC GLAUCOMA
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DOI：
10.1016/j.neuroscience.2009.04.075
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发表时间：
2009-08-18
期刊：
影响因子：
3.3
通讯作者：
So, K. -F.
中科院分区：
文献类型：
--
作者：
Fu, Q. -L.;Li, X.;So, K. -F.
青光眼是一种进行性神经病，其特征是视网膜神经节细胞(RGC)死亡导致视力丧失。目前还没有有效的神经保护剂来治疗这种疾病。众所周知，脑源性神经营养因子(BDNF)可以暂时延缓高眼压眼球RGC的死亡。中枢神经系统特有的富含亮氨酸的重复蛋白LINGO-1参与了对某些营养途径的负调控。因此，我们研究了脑源性神经营养因子联合LINGO-1拮抗剂是否能促进高眼压后RGC的长期存活。在这项研究中，成年大鼠使用Ar激光光凝巩膜上静脉和角膜缘静脉，以提高眼压。在诱导高眼压后4周的长期进展后，BDNF单独对视网膜节细胞显示出轻微的神经保护作用。然而，BDNF和LINGO-1-Fc联合应用可在相同条件下阻止RGC死亡。我们进一步证实：(1)LINGO-1与BDNF受体TrkB在视网膜节细胞中共表达，(2)BDNF与LINGO-1-Fc联合应用比单独使用BDNF能更好地激活视网膜损伤后的TrkB。这些结果表明，BDNF和LINGO-1拮抗剂联合应用可以对慢性高眼压模型中的视网膜神经节细胞起到长期保护作用。TrkB可能是这种神经保护的主要介质。(C)2009年IBRO。爱思唯尔有限公司出版。保留所有权利。
Glaucoma is a progressive neuropathy characterized by loss of vision as a result of retinal ganglion cell (RGC) death. There are no effective neuroprotectants to treat this disorder. Brain-derived neurotrophic factor (BDNF) is well known to transiently delay RGC death in ocular hypertensive eyes. The CNS-specific leucine-rich repeat protein LINGO-1 contributes to the negative regulation to some trophic pathways. We thereby examined whether BDNF combined with LINGO-1 antagonists can promote long-term RGC survival after ocular hypertension. In this study, intraocular pressure was elevated in adult rats using an argon laser to photocoagulate the episcleral and limbal veins. BDNF alone shows slight neuroprotection to RGCs after a long-term progress of 4 weeks following the induction of ocular hypertension. However, combination of BDNF and LINGO-1-Fc prevents RGC death in the same condition. We further identified that (1) LINGO-1 was co-expressed with BDNF receptor, TrkB in the RGCs, and (2) BDNF combined with LINGO-1-Fc activated more TrkB in the injured retina compared to BDNF lone. These results indicate that the combination of BDNF with LINGO-1 antagonist can provide long-term protection for RGCs in a chronic ocular hypertension model. TrkB may be the predominant mediator of this neuroprotection. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.