Neuroprotective effect of geranylgeranylacetone against ischemia-induced retinal injury.
OBJECTIVE
This study was conducted to assess the effects of geranylgeranylacetone (GGA) on ischemia-induced retinal injury.


METHODS
Adult C57BL/6J mice were given oral treatments of GGA at 200 mg/kg daily for seven days. Ischemic retinal injury was carried out, and the extent of retinal cell death was quantitatively examined after 7 days. Immunohistochemistry for single-stranded DNA, phosphorylated form of p38 mitogen-activated protein kinase (p38 MAPK), and cleaved caspase-3 were performed one day after ischemic injury.


RESULTS
In GGA-treated mice, we found the number of surviving retinal neurons was significantly increased compared with vehicle-treated mice. Ischemia-induced phosphorylation of p38 MAPK, which mediates apoptosis of retinal ganglion cells, was suppressed by GGA treatment. In such retinas, cleaved caspase-3- and single-stranded DNA-positive cells were also decreased compared with vehicle-treated mice.


CONCLUSIONS
Oral GGA is a useful treatment for various retinal degenerative diseases that involve ischemic injury.
Harada
Chikako
C
Department of Molecular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, Japan.
Nakamura
Kazuaki
K
Guo
Xiaoli
X
Kitaichi
Nobuyoshi
N
Mitamura
Yoshinori
Y
Yoshida
Kazuhiko
K
Ohno
Shigeaki
S
Yoshida
Hiroshi
H
Harada
Takayuki
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000737:chemistry / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D004277:DNA, Single-Stranded / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D007150:Immunohistochemistry; D007511:Ischemia / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D012160:Retina / Q000187:drug effects* / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D012171:Retinal Vessels; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D004277:DNA, Single-Stranded; D004224:Diterpenes; D018696:Neuroprotective Agents; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; C031049:geranylgeranylacetone