PMID- 24992648 OWN - NLM STAT- MEDLINE DCOM- 20150602 LR - 20211021 IS - 1755-5949 (Electronic) IS - 1755-5930 (Print) IS - 1755-5930 (Linking) VI - 20 IP - 10 DP - 2014 Oct TI - Hepatocyte growth factor promotes long-term survival and axonal regeneration of retinal ganglion cells after optic nerve injury: comparison with CNTF and BDNF. PG - 916-29 LID - 10.1111/cns.12304 [doi] AB - AIMS: Different trophic factors are known to promote retinal ganglion cell survival and regeneration, but each had their own limitations. We report that hepatocyte growth factor (HGF) confers distinct advantages in supporting ganglion cell survival and axonal regeneration, when compared to two well-established trophic factors ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF). METHODS: Ganglion cells in adult hamster were injured by cutting the optic nerve. HGF, CNTF, or BDNF was injected at different dosages intravitreally after injury. Ganglion cell survival was quantified at 7, 14, or 28 days postinjury. Peripheral nerve (PN) grafting to the cut optic nerve of the growth factor-injected eye was performed either immediately after injury or delayed until 7 days post-injury. Expression of heat-shock protein 27 and changes in microglia numbers were quantified in different growth factor groups. The cellular distribution of c-Met in the retina was examined by anti-c-Met immunostaining. RESULTS: Hepatocyte Growth Factor (HGF) was equally potent as BDNF in promoting short-term survival (up to 14 days post-injury) and also supported survival at 28 days post-injury when ganglion cells treated by CNTF or BDNF failed to be sustained. When grafting was performed without delay, HGF stimulated twice the number of axons to regenerate compared with control but was less potent than CNTF. However, in PN grafting delayed for 7 days after optic nerve injury, HGF maintained a better propensity of ganglion cells to regenerate than CNTF. Unlike CNTF, HGF application did not increase HSP27 expression in ganglion cells. Microglia proliferation was prolonged in HGF-treated retinas compared with CNTF or BDNF. C-Met was localized to both ganglion cells and Muller cells, suggesting HGF could be neuroprotective via interacting with both neurons and glia. CONCLUSION: Compared with CNTF or BDNF, HGF is advantageous in sustaining long-term ganglion cell survival and their propensity to respond to favorable stimuli. CI - (c) 2014 John Wiley & Sons Ltd. FAU - Wong, Wai-Kai AU - Wong WK AD - School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China. FAU - Cheung, Anny Wan-Suen AU - Cheung AW FAU - Yu, Sau-Wai AU - Yu SW FAU - Sha, Ou AU - Sha O FAU - Cho, Eric Yu Pang AU - Cho EY LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140703 PL - England TA - CNS Neurosci Ther JT - CNS neuroscience & therapeutics JID - 101473265 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (C-Mel) RN - 0 (Cephalosporins) RN - 0 (Ciliary Neurotrophic Factor) RN - 0 (HSP27 Heat-Shock Proteins) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - Q41OR9510P (Melphalan) SB - IM MH - Animals MH - *Brain-Derived Neurotrophic Factor/pharmacology/therapeutic use MH - Cell Survival MH - Cephalosporins/metabolism MH - *Ciliary Neurotrophic Factor/pharmacology/therapeutic use MH - Cricetinae MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - HSP27 Heat-Shock Proteins/metabolism MH - *Hepatocyte Growth Factor/pharmacology/therapeutic use MH - Melphalan/analogs & derivatives/metabolism MH - Mesocricetus MH - Nerve Regeneration/*drug effects MH - *Optic Nerve Injuries/drug therapy/pathology/physiopathology MH - Retinal Ganglion Cells/*drug effects MH - Time Factors PMC - PMC6493180 OTO - NOTNLM OT - Heat-shock protein OT - Microglia OT - Neuroprotection OT - Optic nerve OT - Retinal ganglion cell OT - Trophic factor COIS- The authors declare no conflict of interest. EDAT- 2014/07/06 06:00 MHDA- 2015/06/03 06:00 PMCR- 2014/07/03 CRDT- 2014/07/04 06:00 PHST- 2013/10/11 00:00 [received] PHST- 2014/06/02 00:00 [revised] PHST- 2014/06/04 00:00 [accepted] PHST- 2014/07/04 06:00 [entrez] PHST- 2014/07/06 06:00 [pubmed] PHST- 2015/06/03 06:00 [medline] PHST- 2014/07/03 00:00 [pmc-release] AID - CNS12304 [pii] AID - 10.1111/cns.12304 [doi] PST - ppublish SO - CNS Neurosci Ther. 2014 Oct;20(10):916-29. doi: 10.1111/cns.12304. Epub 2014 Jul 3.