title: Brain-derived neurotrophic factor inhibits osmotic swelling of rat retinal glial (Müller) and bipolar cells by activation of basic fibroblast growth factor signaling.
abstract: Water accumulation in retinal glial (Müller) and neuronal cells resulting in cellular swelling contributes to the development of retinal edema and neurodegeneration. Intravitreal administration of neurotrophins such as brain-derived neurotrophic factor (BDNF) is known to promote survival of retinal neurons. Here, we show that exogenous BDNF inhibits the osmotic swelling of Müller cell somata induced by superfusion of rat retinal slices or freshly isolated cells with a hypoosmotic solution containing barium ions. BDNF also inhibited the osmotic swelling of bipolar cell somata in retinal slices, but failed to inhibit the osmotic soma swelling of freshly isolated bipolar cells. The inhibitory effect of BDNF on Müller cell swelling was mediated by activation of tropomyosin-related kinase B (TrkB) and transactivation of fibroblast growth factor receptors. Exogenous basic fibroblast growth factor (bFGF) fully inhibited the osmotic swelling of Müller cell somata while it partially inhibited the osmotic swelling of bipolar cell somata. Isolated Müller cells displayed immunoreactivity of truncated TrkB, but not full-length TrkB. Isolated rod bipolar cells displayed immunoreactivities of both TrkB isoforms. Data suggest that the neuroprotective effect of exogenous BDNF in the retina is in part mediated by prevention of the cytotoxic swelling of retinal glial and bipolar cells. While BDNF directly acts on Müller cells by activation of TrkB, BDNF indirectly acts on bipolar cells by inducing glial release of factors like bFGF that inhibit bipolar cell swelling.
authors: Institute of Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany; Paul Flechsig Institute of Brain Research, Medical Faculty, University of Leipzig, Leipzig, Germany.
authors: B-A
authors: BA
authors: Berk
authors: Paul Flechsig Institute of Brain Research, Medical Faculty, University of Leipzig, Leipzig, Germany.
authors: S
authors: S
authors: Vogler
authors: Paul Flechsig Institute of Brain Research, Medical Faculty, University of Leipzig, Leipzig, Germany.
authors: T
authors: T
authors: Pannicke
authors: Paul Flechsig Institute of Brain Research, Medical Faculty, University of Leipzig, Leipzig, Germany.
authors: H
authors: H
authors: Kuhrt
authors: Paul Flechsig Institute of Brain Research, Medical Faculty, University of Leipzig, Leipzig, Germany; Institute of Biological Sciences, Federal University of Pará, Belém, Brazil.
authors: T B
authors: TB
authors: Garcia
authors: Department of Ophthalmology and Eye Hospital, Medical Faculty, University of Leipzig, Leipzig, Germany.
authors: P
authors: P
authors: Wiedemann
authors: Paul Flechsig Institute of Brain Research, Medical Faculty, University of Leipzig, Leipzig, Germany.
authors: A
authors: A
authors: Reichenbach
authors: Institute of Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany.
authors: J
authors: J
authors: Seeger
authors: Department of Ophthalmology and Eye Hospital, Medical Faculty, University of Leipzig, Leipzig, Germany. Electronic address: bria@medizin.uni-leipzig.de.
authors: A
authors: A
authors: Bringmann
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001464:Barium / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology*; D004487:Edema / Q000188:drug therapy* / Q000209:etiology; D063928:Ependymoglial Cells / Q000187:drug effects*; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009997:Osmotic Pressure; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D020813:Receptor, trkB / Q000378:metabolism; D012160:Retina / Q000166:cytology; D051245:Retinal Bipolar Cells / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D001464:Barium; D005346:Fibroblast Growth Factors; D020813:Receptor, trkB; D011493:Protein Kinase C
keywords: bipolar cell; brain-derived neurotrophic factor; cell swelling; glia; osmotic stress; retina