S.M.J.F. and G.G. contributed equally to this work.
bFGF-mediated redox activation of the PI3K/Akt pathway in retinal photoreceptor cells
Article first published online: 11 JAN 2011
© 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 33, Issue 4, pages 632–641, February 2011
How to Cite
Farrell, S. M. J., Groeger, G., Bhatt, L., Finnegan, S., O’Brien, C. J. and Cotter, T. G. (2011), bFGF-mediated redox activation of the PI3K/Akt pathway in retinal photoreceptor cells. European Journal of Neuroscience, 33: 632–641. doi: 10.1111/j.1460-9568.2010.07559.x
- Issue published online: 14 FEB 2011
- Article first published online: 11 JAN 2011
- Received 27 August 2010, revised 4 November 2010, accepted 11 November 2010
- basic fibroblast growth factor;
- reactive oxygen species
In many retinal diseases, it is the death of photoreceptors that leads to blindness. In previous in vitro and in vivo studies, basic fibroblast growth factor (bFGF) has been shown to increase retinal cell survival. More recently, reactive oxygen species (ROS) have also been shown to promote cell survival, contrary to the traditional view that they are solely destructive molecules. Due to this possible link, we hypothesised that bFGF could stimulate the production of ROS, which in turn stimulates the protein kinase B (Akt) survival pathway. Flow cytometry was used to measure the fluorescence of oxidised dihydrorhodamine, a ROS indicator, in the murine 661W photoreceptor cell line under several different conditions. Expression of cyclooxygenase (Cox) enzymes was evaluated by immunohistochemistry, and the response of photoreceptor cells to exogenous bFGF in the explanted mouse retina was studied by confocal microscopy. Exogenous addition of bFGF to 661W cells resulted in an increase in ROS production that lasted for 24 h. When this ROS production was inhibited, bFGF-induced phosphorylation of Akt was prevented. Through the use of inhibitors and small interfering RNA in the cell line, the source of this production was shown to be Cox and to involve the activation of phospholipases A2 + C. This pathway may also occur in the mouse retina, as we showed that the retina expressed Cox1&2, and that photoreceptors in explanted retina respond to bFGF by increasing their ROS levels. These results demonstrate that exogenous bFGF can stimulate ROS production through the activation of Cox, and activate the Akt pathway.