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

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1842

Article

Gupta, Vivek¹  You, Yuyi¹  Li, Jonathan¹  Gupta, Veer²  Golzan, Mojtaba¹  Klistorner, Alexander^1,6  van den Buuse, Maarten^3,4,5  Graham, Stuart^1,6 

[1] Macquarie Univ, Australian Sch Adv Med, Sydney, NSW 2109, Australia

[2] Edith Cowan Univ, Sch Med Sci, Perth, WA, Australia

[3] Morey Inst Neurosci & Mental Hlth, Behav Neurosci Lab, Melbourne, Vic, Australia

[4] Univ Melbourne, Dept Pharmacol, Melbourne, Vic 3010, Australia

[5] La Trobe Univ, Sch Psychol Sci, Melbourne, Vic, Australia

[6] Univ Sydney, Save Sight Inst, Sydney, NSW 2006, Australia

关键词: Brain-derived neurotrophic factor;    TrkB receptor;    Signal transduction;    Ganglion cell layer;    Glaucoma;    Amyloid beta;   

DOI  :  10.1016/j.bbadis.2014.05.026

来源: Elsevier

【 摘 要 】

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 beta 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. (C) 2014 Elsevier B.V. All rights reserved.

【 授权许可】

Free