Nerve growth factor inhibits osmotic swelling of rat retinal glial (Müller) and bipolar cells by inducing glial cytokine release
Article first published online: 8 AUG 2014
© 2014 International Society for Neurochemistry
Journal of Neurochemistry
Volume 131, Issue 3, pages 303–313, November 2014
How to Cite
J. Neurochem. (2014) 131, 303–313.
- Issue published online: 20 OCT 2014
- Article first published online: 8 AUG 2014
- Accepted manuscript online: 17 JUL 2014 02:42AM EST
- Manuscript Accepted: 14 JUL 2014
- Manuscript Revised: 11 JUL 2014
- Manuscript Received: 17 MAR 2014
- Deutsche Forschungsgemeinschaft. Grant Numbers: GRK 1097/1, RE 849/16-1
- bipolar cell;
- cell swelling;
- nerve growth factor;
Osmotic swelling of neurons and glial cells contributes to the development of retinal edema and neurodegeneration. We show that nerve growth factor (NGF) inhibits the swelling of glial (Müller) and bipolar cells in rat retinal slices induced by barium-containing hypoosmotic solution. NGF also reduced Müller and bipolar cell swelling in the post-ischemic retina. On the other hand, NGF prevented the swelling of freshly isolated Müller cells, but not of isolated bipolar cells, suggesting that NGF induces a release of factors from Müller cells that inhibit bipolar cell swelling in retinal slices. The inhibitory effect of NGF on Müller cell swelling was mediated by activation of TrkA (the receptor tyrosine kinase A), but not p75NTR, and was prevented by blockers of metabotropic glutamate, P2Y1, adenosine A1, and fibroblast growth factor receptors. Basic fibroblast growth factor fully inhibited the swelling of freshly isolated Müller cells, but only partially the swelling of isolated bipolar cells. In addition, glial cell line-derived neurotrophic factor and transforming growth factor-β1, but not epidermal growth factor and platelet-derived growth factor, reduced the swelling of bipolar cells. Both Müller and bipolar cells displayed TrkA immunoreactivity, while Müller cells were also immunostained for p75NTR and NGF. The data suggest that the neuroprotective effect of NGF in the retina is in part mediated by prevention of the cytotoxic glial and bipolar cell swelling.
Cytotoxic cell swelling contributes to retinal neurodegeneration. Nerve growth factor (NGF) inhibits the osmotic swelling of glial cells by acting at TrkA, release of bFGF, and opening of K+ and Cl− channels. The NGF-induced glial release of cytokines like bFGF inhibits the osmotic swelling of bipolar cells, suggesting that the neuroprotective effect of NGF is in part mediated by prevention of cytotoxic cell swelling.