TrkB-T1 Receptors on Muller Cells Play Critical Role in Brain-Derived Neurotrophic Factor-Mediated Photoreceptor Protection against Phototoxicity

Abstract

We conclude that Muller cells are one of the cells responsible for the expression of TrkBs, and TrkB-T1 may play a role in the protection of photoreceptors against phototoxicity.

Brain-Derived Neurotrophic Factor in Patients With Age-Related Macular Degeneration and Its Correlation With Retinal Layer Thicknesses

“…52 This supports the possibility that BDNF might induce signaling in other cells of the retina, thus acting indirectly on photoreceptors. 53 Saito et al 54 conducted a study to determine how BDNF protects the photoreceptor against phototoxicity and concluded that BDNF enhanced the expression of TrkB receptors on Müller cells and Müller cells play an important role in the photoreceptor protection from phototoxicity. Regardless of whether BDNF acts directly or indirectly on photoreceptors, this neurotrophin was widely applied to prevent photoreceptor apoptosis.…”

Brain-derived neurotrophic factor inhibits osmotic swelling of rat retinal glial (Müller) and bipolar cells by activation of basic fibroblast growth factor signaling

“…In the retina, the neurotrophic effect of BDNF is in part mediated by a direct action on retinal neurons, e.g., TrkB-expressing retinal ganglion cells and dopaminergic amacrines (Cellerino and Kohler, 1997;Suzuki et al, 1998;Hirsch et al, 2000;Asai et al, 2007), and by an indirect mechanism involving Mu¨ller cells (Wexler et al, 1998;Wahlin et al, 2000Wahlin et al, , 2001Harada et al, 2002;Saito et al, 2009). However, it was shown that TrkB signaling in Mu¨ller cells, but not in retinal ganglion and amacrine cells, is critically involved in neural protection and regeneration during retinal degeneration (Harada et al, 2011) and that the BDNF-induced protection of photoreceptors from light damage is mediated by activation of truncated TrkB expressed by Mu¨ller cells (Saito et al, 2009). We found that freshly isolated Mu¨ller cells display immunoreactivity of the truncated (Fig.…”

“…Intravitreal administration of various growth factors, cytokines, and neurotrophins including brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and basic fibroblast growth factor (bFGF) was shown to promote the survival of photoreceptors and retinal neurons under pathological conditions (Faktorovich et al, 1992;LaVail et al, 1992;Unoki and LaVail, 1994;Mansour-Robaey et al, 1994;Harada et al, 2000;Hauck et al, 2006;reviewed in Bringmann et al, 2009). The neurotrophic rescue of photoreceptors and neurons is, at least in part, indirectly mediated by regulation of the trophic factor production in retinal glial (Mu¨ller) cells (Wexler et al, 1998;Wahlin et al, 2000;Harada et al, 2002;Saito et al, 2009). Mu¨ller cells are known to produce various neuroprotective factors including BDNF, bFGF, NGF, and GDNF (Harada et al, 2000(Harada et al, , 2002Seki et al, 2005;Hauck et al, 2006;Garcia et al, 2014).…”

Light-induced retinal injury enhanced neurotrophins secretion and neurotrophic effect of mesenchymal stem cells in vitro

“…Both fibroblast growth factor receptor (FGFR) and CNTFRα are localized on photoreceptors suggesting direct effects of these two neurotrophins on photoreceptors (17) . Although BDNF do not impact directly on photoreceptors, it has photoreceptor rescue effect though the activation of glial cell (18) . Thus these neurotrophic factors were selected in our study.…”