Effect of geranylgeranylacetone on optic neuritis in experimental autoimmune encephalomyelitis.
Optic neuritis is an acute inflammatory demyelinating syndrome of the central nervous system (CNS) that often occurs in multiple sclerosis (MS). Since it can cause irreversible visual loss, especially in the optic-spinal form of MS or neuromyelitis optica (NMO), the present study was conducted to assess the effects of geranylgeranylacetone (GGA) on optic neuritis in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Myelin oligodendrocyte glycoprotein-induced EAE mice received oral administration of GGA at 500 mg/kg or vehicle once daily for 22 days. The effects of GGA on the severity of optic neuritis were examined by morphological analysis on day 22. Visual functions were measured by the multifocal electroretinograms (mfERG). In addition, the effects of GGA on severity of myelitis were monitored both on clinical signs and morphological aspects. The visual function, as assessed by the second-kernel of mfERG, was significantly improved in GGA-treated mice compared with vehicle-treated mice. GGA treatment decreased the number of degenerating axons in the optic nerve and prevented cell loss in the retinal ganglion cell layer. However, the severity of demyelination in the spinal cord remained unaffected with the treatment of GGA. These results suggest that oral GGA administration has beneficial effect on the treatment for optic neuritis in the EAE mouse model of MS.
Guo
Xiaoli
X
Department of Molecular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, Japan.
Harada
Chikako
C
Namekata
Kazuhiko
K
Kikushima
Kenji
K
Mitamura
Yoshinori
Y
Yoshida
Hiroshi
H
Matsumoto
Yoh
Y
Harada
Takayuki
T
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D004224:Diterpenes / Q000627:therapeutic use*; D004596:Electroretinography; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009900:Optic Nerve / Q000187:drug effects / Q000473:pathology; D009902:Optic Neuritis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D004224:Diterpenes; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; C031049:geranylgeranylacetone