title: BDNF impairment is associated with age-related changes in the inner retina and exacerbates experimental glaucoma.
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(+/-) mice and compared it with wild type controls. This study demonstrated that BDNF(+/-) 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(+/-) 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.
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Australia. Electronic address: vivek.gupta@mq.edu.au.
authors.forename: Vivek
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Australia.
authors.forename: Yuyi
authors.initials: Y
authors.lastname: You
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Medical Sciences, Edith Cowan University, Perth, Australia.
authors.forename: Veer
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Australia.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Golzan
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Australia; Save Sight Institute, Sydney University, Australia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Klistorner
authors.affiliation: Behavioural Neuroscience Laboratory, Florey Institute for Neuroscience and Mental Health, Melbourne, Australia; Department of Pharmacology, University of Melbourne, Australia; School of Psychological Science, La Trobe University, Melbourne, Australia.
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Buuse
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Australia; Save Sight Institute, Sydney University, Australia.
authors.forename: Stuart
authors.initials: S
authors.lastname: Graham
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001344:Autopsy; D001370:Axonal Transport; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D016022:Case-Control Studies; D004195:Disease Models, Animal; D004596:Electroretinography; D004797:Enzyme-Linked Immunosorbent Assay; D005901:Glaucoma / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D018345:Mice, Knockout; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000378:metabolism*; D020813:Receptor, trkB / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction
chemical_list: D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D020813:Receptor, trkB
keywords: Amyloid beta; Brain-derived neurotrophic factor; Ganglion cell layer; Glaucoma; Signal transduction; TrkB receptor