Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8260196 | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | 2014 | 12 Pages |
Abstract
Brain-derived neurotrophic factor (BDNF) stimulation of its high-affinity receptor TrkB results in activation of pro-survival cell-signalling pathways that can afford neuroprotection to the retina. Reduction in retrograde axonal transport of neurotrophic factors such as BDNF from the brain to the neuronal cell bodies in the retina has been suggested as a critical factor underlying progressive and selective degeneration of ganglion cell layer and optic nerve in glaucoma. We investigated the role of BDNF in preserving inner retinal homeostasis in normal and glaucoma states using BDNF+/â mice and compared it with wild type controls. This study demonstrated that BDNF+/â animals were more susceptible to functional, morphological and molecular degenerative changes in the inner retina caused by age as well as upon exposure to experimental glaucoma caused by increased intraocular pressure. Glaucoma induced a down regulation of BDNF/TrkB signalling and an increase in levels of neurotoxic amyloid β 1-42 in the optic nerve head which were exacerbated in BDNF+/â mice. Similar results were obtained upon analysing the human optic nerve head tissues. Our data highlighted the role of BDNF in maintaining the inner retinal integrity under normal conditions and the detrimental effects of its insufficiency on the retina and optic nerve in glaucoma.
Keywords
PI3KONHiOpTrkBGCLAPPRGCERGBDNFH&Eelectroretinogramamyloid betaOptic nerve headRetinal ganglion cellsbrain derived neurotrophic factorBrain-derived neurotrophic factorphosphatidylinositol 3 kinaseIntraocular pressureganglion cell layerPSTRSignal transductionhaematoxylin and eosinamyloid precursor proteinGlaucomaTrkB receptor
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Authors
Vivek Gupta, Yuyi You, Jonathan Li, Veer Gupta, Mojtaba Golzan, Alexander Klistorner, Maarten van den Buuse, Stuart Graham,