Abstract

P 206

Retinal activation of the CREB-dependent genes c-Fos and Bcl-2 following acute and chronic optic nerve damage

Christian Mawrin1, Christian Vorwerk2
1Institut für Neuropathologie, Otto-von-Guericke-Universität, Magdeburg; 2Universitäts-Augenklinik, Otto-von-Guericke-Universität, Magdeburg

Objective
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 models of acute and chronic optic nerve damage.
Methods
Retinal tissue from six rhesus monkeys (with chronic mild or moderate glaucomatous damage was studied for the expression of pMAPK, pAkt, pCREB, c-Fos and bcl-2 by immunohistochemistry. Additionally, 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
Retinal tissue from Rhesus monkeys (bulbi were a gift from Prof. Hernandez, St. Louis, USA) showed an increase of pMAPK and pCREB-positive cells in the ganglion cell layer (GCL) and inner nuclear layer (INL), while pAkt-positive cell were reduced compared to the control eye. c-Fos staining was enhanced in glaucomatous eyes, but Bcl-2 staining was clearly reduced. 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. Chronic glaucomatous retinal ganglion cell damage results in activation of the MAP-Kinase/CREB- signalling, as possible mediator of apoptotic retinal ganglion cell death.

Copyright: 2009 Porstmann Kongresse GmbH. All rights reserved. Impressum, Disclaimer.