Neuroprotective effect of geranylgeranylacetone against ischemia-induced retinal injury.

PURPOSE 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.