title: Nerve growth factor inhibits osmotic swelling of rat retinal glial (Müller) and bipolar cells by inducing glial cytokine release.
abstract: 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 p75(NTR) , 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 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. 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.
authors.affiliation: Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany; Institute of Biological Sciences, Federal University of Pará, Belém, Brazil.
authors.forename: Tarcyane Barata
authors.initials: TB
authors.lastname: Garcia
authors.forename: Thomas
authors.initials: T
authors.lastname: Pannicke
authors.forename: Stefanie
authors.initials: S
authors.lastname: Vogler
authors.forename: Benjamin-Andreas
authors.initials: BA
authors.lastname: Berk
authors.forename: Antje
authors.initials: A
authors.lastname: Grosche
authors.forename: Peter
authors.initials: P
authors.lastname: Wiedemann
authors.forename: Johannes
authors.initials: J
authors.lastname: Seeger
authors.forename: Andreas
authors.initials: A
authors.lastname: Reichenbach
authors.forename: Anderson Manoel
authors.initials: AM
authors.lastname: Herculano
authors.forename: Andreas
authors.initials: A
authors.lastname: Bringmann
mesh_terms: D000818:Animals; D048429:Cell Size / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005346:Fibroblast Growth Factors / Q000502:physiology; D008297:Male; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism*; D009997:Osmotic Pressure; D051381:Rats; D020318:Rats, Long-Evans; D017475:Receptors, Nerve Growth Factor / Q000187:drug effects; D051245:Retinal Bipolar Cells / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D016207:Cytokines; D017475:Receptors, Nerve Growth Factor; D005346:Fibroblast Growth Factors; D020932:Nerve Growth Factor
keywords: bipolar cell; cell swelling; glial; ischemia; nerve growth factor; retina