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We report that hepatocyte growth factor (<jats:styled-content style=\"fixed-case\">HGF<\/jats:styled-content>) confers distinct advantages in supporting ganglion cell survival and axonal regeneration, when compared to two well\u2010established trophic factors ciliary neurotrophic factor (<jats:styled-content style=\"fixed-case\">CNTF<\/jats:styled-content>) and brain\u2010derived neurotrophic factor (BDNF).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ganglion cells in adult hamster were injured by cutting the optic nerve. <jats:styled-content style=\"fixed-case\">HGF<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> CNTF<\/jats:styled-content>, or <jats:styled-content style=\"fixed-case\">BDNF<\/jats:styled-content> was injected at different dosages intravitreally after injury. Ganglion cell survival was quantified at 7, 14, or 28\u00a0days postinjury. Peripheral nerve (<jats:styled-content style=\"fixed-case\">PN<\/jats:styled-content>) grafting to the cut optic nerve of the growth factor\u2013injected eye was performed either immediately after injury or delayed until 7\u00a0days post\u2010injury. Expression of heat\u2010shock protein 27 and changes in microglia numbers were quantified in different growth factor groups. The cellular distribution of c\u2010Met in the retina was examined by anti\u2010c\u2010Met immunostaining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Hepatocyte Growth Factor (HGF) was equally potent as <jats:styled-content style=\"fixed-case\">BDNF<\/jats:styled-content> in promoting short\u2010term survival (up to 14\u00a0days post\u2010injury) and also supported survival at 28\u00a0days post\u2010injury when ganglion cells treated by <jats:styled-content style=\"fixed-case\">CNTF<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">BDNF<\/jats:styled-content> failed to be sustained. When grafting was performed without delay, <jats:styled-content style=\"fixed-case\">HGF<\/jats:styled-content> stimulated twice the number of axons to regenerate compared with control but was less potent than <jats:styled-content style=\"fixed-case\">CNTF<\/jats:styled-content>. However, in <jats:styled-content style=\"fixed-case\">PN<\/jats:styled-content> grafting delayed for 7\u00a0days after optic nerve injury, <jats:styled-content style=\"fixed-case\">HGF<\/jats:styled-content> maintained a better propensity of ganglion cells to regenerate than <jats:styled-content style=\"fixed-case\">CNTF<\/jats:styled-content>. Unlike <jats:styled-content style=\"fixed-case\">CNTF<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> HGF<\/jats:styled-content> application did not increase <jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>27 expression in ganglion cells. Microglia proliferation was prolonged in <jats:styled-content style=\"fixed-case\">HGF<\/jats:styled-content>\u2010treated retinas compared with <jats:styled-content style=\"fixed-case\">CNTF<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">BDNF<\/jats:styled-content>. C\u2010Met was localized to both ganglion cells and Muller cells, suggesting <jats:styled-content style=\"fixed-case\">HGF<\/jats:styled-content> could be neuroprotective via interacting with both neurons and glia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Compared with <jats:styled-content style=\"fixed-case\">CNTF<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">BDNF<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> HGF<\/jats:styled-content> is advantageous in sustaining long\u2010term ganglion cell survival and their propensity to respond to favorable stimuli.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12304","type":"journal-article","created":{"date-parts":[[2014,7,3]],"date-time":"2014-07-03T08:51:03Z","timestamp":1404377463000},"page":"916-929","source":"Crossref","is-referenced-by-count":28,"title":["Hepatocyte Growth Factor Promotes Long\u2010Term Survival and Axonal Regeneration of Retinal Ganglion Cells after Optic Nerve Injury: Comparison with <scp>CNTF<\/scp> and <scp>BDNF<\/scp>"],"prefix":"10.1111","volume":"20","author":[{"given":"Wai\u2010Kai","family":"Wong","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences The Chinese University of Hong Kong Shatin Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anny Wan\u2010Suen","family":"Cheung","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The Chinese University of Hong Kong Shatin Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sau\u2010Wai","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The Chinese University of Hong Kong Shatin Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ou","family":"Sha","sequence":"additional","affiliation":[{"name":"Department of Preclinical Medicine School of Medicine Shenzhen University Guangdong 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