title: Neuroprotective and neurite outgrowth effects of maltol on retinal ganglion cells under oxidative stress.
abstract: OBJECTIVE
  To evaluate the neuroprotective and neurite outgrowth effects of maltol, a natural aroma compound, on retinal ganglion cells (RGCs) under oxidative stress in vitro.
  
  
  METHODS
  Mouse primary RGCs were isolated using immunopanning-magnetic separation and exposed to H2O2 in the presence of maltol. The cell viability and apoptosis were determined by using adenosine 5'-triphosphate (ATP) assay and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), respectively. Neurite outgrowth was assessed by immunofluorescence for α-tubulin. The activation of nuclear factor-κB (NF-κB) was also evaluated using immunofluorescence.
  
  
  RESULTS
  When the RGCs were exposed to 20 μM of H2O2 for 16 h, their viability dropped to 40.3±3.4%. However, the maltol treatment restored the cells in a dose-dependent manner. The viability recovered to 73.9±5.1% with 10 μM of maltol and even reached 175.1±11.3% with 2 mM of maltol, as measured by ATP assay. This oxidative stress significantly increased the number of TUNEL-positive RGCs, but the maltol drastically reduced the proportion of those apoptotic cells. The oxidative stress hampered the neurite outgrowth of the RGCs, whereas maltol restored their ability to sprout neurites. Regarding NF-κB, the active form of phosphorylated NF-κB (pNF-κB) increased the oxidative stress level but the maltol treatment again reduced it to an unstressful level.
  
  
  CONCLUSIONS
  Our data revealed that maltol attenuated the oxidative stress-induced injury in the primary mouse RGCs. Its neuroprotective and neurite outgrowth effects seemed to be related to NF-κB signaling. Maltol has potential as a new neuroprotective therapeutic agent for oxidative stress-related ocular diseases, including glaucoma.
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Samin
authors.initials: S
authors.lastname: Hong
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Iizuka
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Taekjune
authors.initials: T
authors.lastname: Lee
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Chan Yun
authors.initials: CY
authors.lastname: Kim
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Gong Je
authors.initials: GJ
authors.lastname: Seong
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D061251:Primary Cell Culture; D011753:Pyrones / Q000494:pharmacology*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D018696:Neuroprotective Agents; D011753:Pyrones; D014404:Tubulin; C008316:maltol; D006861:Hydrogen Peroxide