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.
Keywords
Amyloid beta, Brain-derived neurotrophic factor, Ganglion cell layer, Glaucoma, Signal transduction, TrkB receptor, amyloid beta protein[1-42], brain derived neurotrophic factor, brain derived neurotrophic factor receptor, neurotrophin, animal experiment, animal tissue, article, controlled study, down regulation, enzyme linked immunosorbent assay, experimental glaucoma, human, human tissue, mouse, nonhuman, optic nerve, polyacrylamide gel electrophoresis, priority journal, protein phosphorylation, retina, signal transduction, Western blotting, wild type, age, animal model, Article, glaucoma, inner retina, intraocular pressure, retina ganglion cell, Amyloid beta, Brain-derived neurotrophic factor, Ganglion cell layer, Glaucoma, Signal transduction, TrkB receptor, Age Factors, Aged, Aged, 80 and over, Amyloid beta-Peptides, Animals, Autopsy, Axonal Transport, Blotting, Western, Brain-Derived Neurotrophic Factor, Case-Control Studies, Disease Models, Animal, Electroretinography, Enzyme-Linked Immunosorbent Assay, Glaucoma, Humans, Immunoenzyme Techniques, Mice, Mice, Knockout, Optic Nerve, Peptide Fragments, Receptor, trkB, Retina, Retinal Ganglion Cells, Signal Transduction
Document Type
Journal Article
Date of Publication
1-1-2014
Faculty
Faculty of Health, Engineering and Science
Publisher
Elsevier
School
School of Medical Sciences
RAS ID
19252
Copyright
free_to_read
Comments
Gupta V., You Y., Li J., Gupta V., Golzan M., Klistorner A., van den Buuse M., Graham S. (2014). BDNF impairment is associated with age-related changes in the inner retina and exacerbates experimental glaucoma. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1842(9), 1567-1578. Available here