The mechanism of metabolic and autophagic dysfunction in optic nerve degeneration
Description: Autophagic and metabolic function may decrease in aging. We previously reported the impairment of autophagic flux in optic nerve in glaucomatous optic neuropathy model. Thus, in the present term, we tested if some autophagy activators alter axon loss in tumor necrosis factor (TNF)-induced optic nerve degeneration. First, we found that a SIRT1 activator enhanced autophagic flux and exerted axonal protection. Second, exogenous nicotinamide riboside (NR) upregulated endogenous nicotinamide riboside kinase 1 (NRK1) and SIRT1 expression in optic nerve. NR also enhanced autophagic flux and exerted axonal protection. We also found NRK1 exists in RGCs and optic nerve fibers. Third, we found upregulation of phosphorylated p38 in optic nerve axons in TNF-induced optic nerve degeneration. Upregulated p-p38 may inhibit autophagy. Akebia saponin D, an autophagy activator, prevented the increment of p-p38, enhanced autophagy flux, and exerted axonal protection.
Amount: ¥4,420,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (C)
Start date: 2018-04-01
End date: 2021-03-31
Investigator: Yasushi Kitaoka
Institution: St. Marianna University School of Medicine
Funded outputs count: 4
Funder award ID: 18K09427
OpenAlex ID: G6932287359