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S.M. Ghazi-Nouri, D.G. Charteris, S.E. Moss, G.A. Limb; Production of Brain Derived Neurotrophic Factor by Human Müller Cells and its Upregulation by Platelet Derived Growth Factor . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2244.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The source of neurotrophins (NTs) and their fate in human retina is not fully understood. Brain derived neurotrophic factor (BDNF) is a neurotrophin important in retinal ganglion cell survival. It acts via Tropomyosin-related Kinase B (TrkB) belonging to the protein kinase family. We investigated expression of BDNF and TrkB by cultured human Müller cells. Methods: Human Müller cell primary cultures and the human Müller cell line MIO-M1 (Moorfields Institute of Ophthalmology -Müller 1) were incubated in the presence or absence of platelet derived growth factor (PDGF). Cell lysates were examined for gene expression of BDNF and TrkB using RT-PCR. Fixed cell preparations were investigated for protein presence by immuno-cytochemical methods. Results: Expression of mRNA coding for BDNF and the truncated form of TrkB (t-TrkB) were observed in both primary Müller cell cultures and the MIO-M1 cell line. The full-length form of TrkB was not detected at mRNA level. Addition of PDGF to the culture medium caused a marked increase in the expression of BDNF mRNA but not of t-TrkB mRNA. Staining for BDNF and t-TrkB was also observed around the nucleus in a characteristic granular pattern. Conclusions: These findings suggest that by producing BDNF, Müller cells may support neural survival. Since t-TrkB in the central nervous system internalises BDNF, Müller cells may also be capable of receptor-mediated endocytosis of NTs. This function has important implications in conditions such as retinal detachment where there is Müller cell proliferation. Internalised NT may be stored for recycling or degraded leading to reduced local availability. Up-regulation of BDNF expression by PDGF would also suggest a neuro-protective role for these cells in retinal injury where there is increased PDGF availability. Müller cells in human retina have the potential to control trophic support to neurons via their effects on neurotrophin metabolism.
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