Neuroprotective effect of geranylgeranylacetone against ischemia-induced retinal injury.

Abstract

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.

• Authors: Chikako Harada, Kazuaki Nakamura, Xiaoli Guo, Nobuyoshi Kitaichi, Yoshinori Mitamura, Kazuhiko Yoshida, Shigeaki Ohno, Hiroshi Yoshida, Takayuki Harada
• Journal: Molecular vision (Mol Vis) Vol. 13 Pg. 1601-7 (Sep 07 2007) ISSN: 1090-0535 [Electronic] United States
• PMID: 17893661 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Single-Stranded
• Diterpenes
• Neuroprotective Agents
• p38 Mitogen-Activated Protein Kinases
• Caspase 3
• geranylgeranylacetone

Topics

• Animals
• Apoptosis (drug effects)
• Caspase 3 (chemistry, metabolism)
• Cell Count
• Cell Survival (drug effects)
• DNA, Single-Stranded (metabolism)
• Diterpenes (pharmacology)
• Immunohistochemistry
• Ischemia (pathology, physiopathology)
• Mice
• Mice, Inbred C57BL
• Neuroprotective Agents (pharmacology)
• Phosphorylation (drug effects)
• Retina (drug effects, pathology)
• Retinal Ganglion Cells (drug effects, pathology)
• Retinal Vessels
• p38 Mitogen-Activated Protein Kinases (metabolism)