PMID- 19422885 OWN - NLM STAT- MEDLINE DCOM- 20090916 LR - 20230513 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 162 IP - 2 DP - 2009 Aug 18 TI - Combined effect of brain-derived neurotrophic factor and LINGO-1 fusion protein on long-term survival of retinal ganglion cells in chronic glaucoma. PG - 375-82 LID - 10.1016/j.neuroscience.2009.04.075 [doi] AB - 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 alone. 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. FAU - Fu, Q-L AU - Fu QL AD - Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Road II, Guangzhou, Guangdong, 510080, PR China. FAU - Li, X AU - Li X FAU - Yip, H K AU - Yip HK FAU - Shao, Z AU - Shao Z FAU - Wu, W AU - Wu W FAU - Mi, S AU - Mi S FAU - So, K-F AU - So KF LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090505 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (LINGO1 protein, human) RN - 0 (Membrane Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neuroprotective Agents) RN - 0 (Recombinant Fusion Proteins) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*pharmacology/therapeutic use MH - Cell Survival/drug effects MH - Drug Therapy, Combination MH - Enzyme Activation MH - Female MH - Glaucoma/*drug therapy/pathology/physiopathology MH - Humans MH - Immunoglobulin Fc Fragments/genetics MH - Intraocular Pressure/drug effects MH - Membrane Proteins/biosynthesis/*genetics MH - Nerve Tissue Proteins/biosynthesis/*genetics MH - Neuroprotective Agents/*pharmacology/therapeutic use MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, trkB/biosynthesis MH - Recombinant Fusion Proteins/*pharmacology/therapeutic use MH - Retinal Ganglion Cells/*drug effects/pathology EDAT- 2009/05/09 09:00 MHDA- 2009/09/17 06:00 CRDT- 2009/05/09 09:00 PHST- 2009/03/10 00:00 [received] PHST- 2009/04/22 00:00 [revised] PHST- 2009/04/26 00:00 [accepted] PHST- 2009/05/09 09:00 [entrez] PHST- 2009/05/09 09:00 [pubmed] PHST- 2009/09/17 06:00 [medline] AID - S0306-4522(09)00713-1 [pii] AID - 10.1016/j.neuroscience.2009.04.075 [doi] PST - ppublish SO - Neuroscience. 2009 Aug 18;162(2):375-82. doi: 10.1016/j.neuroscience.2009.04.075. Epub 2009 May 5.