BDNF impairment is associated with age-related changes in the inner retina and exacerbates experimental glaucoma

Vivek Gupta, Yuyi You, Jonathan Li, Veer Gupta, Mojtaba Golzan, Alexander Klistorner, Maarten van den Buuse, Stuart Graham

    Research output: Contribution to journalArticle

    67 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)1567-1578
    Number of pages12
    JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
    Volume1842
    Issue number9
    DOIs
    Publication statusPublished - Sep 2014

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