title: Hepatocyte growth factor promotes long-term survival and axonal regeneration of retinal ganglion cells after optic nerve injury: comparison with CNTF and BDNF.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Compared with CNTF or BDNF, HGF is advantageous in sustaining long-term ganglion cell survival and their propensity to respond to favorable stimuli.
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors.forename: Wai-Kai
authors.initials: WK
authors.lastname: Wong
authors.forename: Anny Wan-Suen
authors.initials: AW
authors.lastname: Cheung
authors.forename: Sau-Wai
authors.initials: SW
authors.lastname: Yu
authors.forename: Ou
authors.initials: O
authors.lastname: Sha
authors.forename: Eric Yu Pang
authors.initials: EY
authors.lastname: Cho
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology / Q000627:therapeutic use; D002470:Cell Survival; D002511:Cephalosporins / Q000378:metabolism; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology / Q000627:therapeutic use; D006224:Cricetinae; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology / Q000627:therapeutic use; D008558:Melphalan / Q000031:analogs & derivatives / Q000378:metabolism; D008647:Mesocricetus; D009416:Nerve Regeneration / Q000187:drug effects*; D020221:Optic Nerve Injuries / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D012165:Retinal Ganglion Cells / Q000187:drug effects*; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C112055:C-Mel; D002511:Cephalosporins; D020934:Ciliary Neurotrophic Factor; D055551:HSP27 Heat-Shock Proteins; D017228:Hepatocyte Growth Factor; D008558:Melphalan
keywords: Heat-shock protein; Microglia; Neuroprotection; Optic nerve; Retinal ganglion cell; Trophic factor