Abstract
Purpose: :
To determine the role of mitogen-activated protein kinase (MAPK)-dependent cAMP response element binding protein (CREB) activation on c-Fos and Bcl-2 gene expression in animal model of acute optic nerve damage.
Methods: :
An rat model of acute optic nerve crush was used to study the time course of pMAPK, pAkt, pCREB, c-Fos and bcl-2 expression by immunohistochemistry, western blotting, and real-time PCR. Ganglion cell death was evaluated by Fluoro-Jade and TUNEL staining.
Results: :
Evaluation of the time course in acute optic nerve damage revealed an activation of pMAPK and pCREB but a depression of pAkt expression. Real-time PCR showed that the pMAPK-pCREB activation is associated with increased c-Fos mRNA but reduced Bcl-2 mRNA levels.
Conclusions: :
Retinal ganglion cell death in the early phase after acute optic nerve trauma is due to an imbalance of pro- and anti-apoptotic signal cascades. With progressing time neuroprotective, anti-apoptotic factors, such as BCL-2 are activated to minimize secondary injury.
Keywords: optic nerve • apoptosis/cell death • ganglion cells