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Samin Hong, Yookyung Song, Gong Je Seong; Neuroprotective effects of maltol on experimental glaucoma models. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2424.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the neuroprotective effects of maltol, a natural aroma compound, on experimental glaucoma models.
For the in vitro study, mouse primary retinal ganglion cells (mRGCs) were isolated using immunopanning-magnetic separation and exposed to hydrogen peroxide (H2O2) in the presence of maltol. For the in vivo study, a total of 45 adult male C57BL/6 mice were used. The left optic nerve of each mouse was crushed for 10 seconds using self-closing forceps. 100 mg/kg of maltol was intraperitoneally injected for 5 consecutive days before (pre-treatment group, n=15) and after (post-treatment group, n=15) the crush injury. The RGC viability and apoptosis were determined by adenosine 5′-triphosphate (ATP) assay and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), respectively. The neurite outgrowth was assessed by immunofluorescence for α-tubulin. The activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs; JNK, ERK, and p38) was also evaluated using immunofluorescence.
When the primary mRGCs were exposed to 20 μM of H2O2 for 16 hours, their viability dropped to 40.3±3.4%. However, the maltol 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. For both the in vitro and in vivo models, the glaucomatous injuries radically increased the number of TUNEL-positive mRGCs, but the maltol significantly reduced the proportion of those apoptotic cells. The active phosphorylated form of NF-κB and MAPKs was increased by the injuries but the maltol reduced it to an unstressful level.
Our data revealed that maltol attenuated the glaucomatous injuries in vitro and in vivo. Its neuroprotective effects seemed to be related to NF-κB and MAPKs signaling. Maltol has a potentiality to be used as a new neuroprotective therapeutic agent for glaucoma.
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