June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Essential Role of Brain Derived Neurotrophic Factor in the Preservation of Retinal Ganglion Cell Function
Author Affiliations & Notes
  • Vivek Kumar Gupta
    Australian school of Advanced Medicine, Macquarie university, Sydney, NSW, Australia
  • Jonathan Li
    Australian school of Advanced Medicine, Macquarie university, Sydney, NSW, Australia
  • Yuyi You
    Australian school of Advanced Medicine, Macquarie university, Sydney, NSW, Australia
  • Maarten van den Buuse
    Behavioural Neuroscience Laboratory, Mental Health Research Institute, University of Melbourne, Melbourne, VIC, Australia
    Department of Pharmacology, University of Melbourne, Melbourne, VIC, Australia
  • Stuart Graham
    Australian school of Advanced Medicine, Macquarie university, Sydney, NSW, Australia
    Save Sight Institute, Sydney university, Sydney, NSW, Australia
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 428. doi:
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      Vivek Kumar Gupta, Jonathan Li, Yuyi You, Maarten van den Buuse, Stuart Graham; Essential Role of Brain Derived Neurotrophic Factor in the Preservation of Retinal Ganglion Cell Function. Invest. Ophthalmol. Vis. Sci. 2013;54(15):428.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Brain derived neurotrophic factor (BDNF) is a high affinity ligand for the Tropomyosin related kinase B (TrkB) receptor. BDNF stimulation triggers TrkB dimerization and autophosphorylation resulting in activation of pro-survival cell-signalling pathways that can afford neuroprotection to the brain and retina. Our previous studies suggest that BDNF/TrkB signalling plays an important role in the retinal ganglion cell (RGC) protection under normal conditions and in glaucoma. We investigated the role of BDNF in whole retina and ganglion cell layer (GCL) homeostasis in vivo using BDNF heterozygous mice. BDNF interaction with the TrkB receptor in retinal ganglion cells under normal and experimental glaucoma conditions was investigated in a rat ocular hypertensive model.

Methods: Wild type and BDNF heterozygous mice were assessed using the scotopic electroretinogram (ERG) and scotopic threshold response (STR). Retinal structure was evaluated by H & E staining. An ocular hypertension model was established in rats using microbead injections. Rat RGCs were isolated using CD90.1 magnetic separation technique from normal and ocular hypertensive rats. The binding of BDNF with TrkB receptor in RGCs was determined using 1D nanoLC ESI-MS/MS mass spectroscopic analysis. TrkB receptor immunoprecipitations were carried out in the RGC lysates.

Results: The partial genetic ablation of BDNF manifested itself in the form of a retinal phenotype depicting a mild preferential loss of STR in the BDNF+/- compared to the wild type animals (p<0.02). No changes were observed in the scotopic ERGs of these BDNF deficient mice. Interestingly, the functional changes were not accompanied by anatomical changes in the GCL of these mice at 4 months of age. At the molecular level, BDNF was observed to physically interact with TrkB receptor in the isolated rat RGCs and BDNF expression was upregulated in response to chronically increased intraocular pressure (IOP) ((p<0.05).

Conclusions: Our studies on BDNF+/- mice reveal that normal levels of BDNF are critical for the preferential preservation of GCL physiology in the retina as determined by STR integrity. Further testing with increasing age will determine if there are longitudinal changes in function or structure. BDNF physically interacts with the TrkB receptor in the RGCs which may facilitate its neuroprotective role.

Keywords: 531 ganglion cells • 615 neuroprotection • 691 retina: proximal (bipolar, amacrine, and ganglion cells)  
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