Nerve growth factor inhibits osmotic swelling of rat retinal glial (Muller) and bipolar cells by inducing glial cytokine release

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 (Muller) and bipolar cells in rat retinal slices induced by barium-containing hypoosmotic solution. NGF also reduced Muller and bipolar cell swelling in the post-ischemic retina. On the other hand, NGF prevented the swelling of freshly isolated Muller cells, but not of isolated bipolar cells, suggesting that NGF induces a release of factors from Muller cells that inhibit bipolar cell swelling in retinal slices. The inhibitory effect of NGF on Muller cell swelling was mediated by activation of TrkA (the receptor tyrosine kinase A), but not p75(NTR), and was prevented by blockers of metabotropic glutamate, P2Y(1), adenosine A(1), and fibroblast growth factor receptors. Basic fibroblast growth factor fully inhibited the swelling of freshly isolated Muller cells, but only partially the swelling of isolated bipolar cells. In addition, glial cell line-derived neurotrophic factor and transforming growth factor-1, but not epidermal growth factor and platelet-derived growth factor, reduced the swelling of bipolar cells. Both Muller and bipolar cells displayed TrkA immunoreactivity, while Muller cells were also immunostained for p75(NTR) 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.