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BDNF impairment is associated with age-related changes in the inner retina and exacerbates experimental glaucoma
journal contribution
posted on 2023-01-30, 04:53 authored by V Gupta, Y You, J Li, Veer GuptaVeer Gupta, M Golzan, A Klistorner, M van den Buuse, S GrahamBrain-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. © 2014 Elsevier B.V.
History
Journal
Biochimica et Biophysica Acta - Molecular Basis of DiseaseVolume
1842Pagination
1567 - 1578Publisher DOI
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ISSN
0925-4439eISSN
1879-260XPublication classification
C1.1 Refereed article in a scholarly journalUsage metrics
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Science & TechnologyLife Sciences & BiomedicineBiochemistry & Molecular BiologyBiophysicsCell BiologyBrain-derived neurotrophic factorTrkB receptorSignal transductionGanglion cell layerGlaucomaAmyloid betaAMYLOID PRECURSOR PROTEINRETROGRADE AXONAL-TRANSPORTOPEN-ANGLE GLAUCOMANEUROTROPHIC FACTOR BDNFGANGLION-CELL SURVIVALALZHEIMERS-DISEASEOPTIC-NERVEIN-VIVOMESSENGER-RNA
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