September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Brain-Derived Neurotrophic Factor Protects Retinal Ganglion Cells and Visual Functions in Mice with Long-Term Ocular Hypertension
Author Affiliations & Notes
  • Liang Feng
    Northwestern University, Evanston, Illinois, United States
  • Hui Chen
    Northwestern University, Evanston, Illinois, United States
  • Ji Yi
    Northwestern University, Evanston, Illinois, United States
  • Hao F Zhang
    Northwestern University, Evanston, Illinois, United States
  • Xiaorong Liu
    Northwestern University, Evanston, Illinois, United States
  • Footnotes
    Commercial Relationships   Liang Feng, None; Hui Chen, None; Ji Yi, None; Hao Zhang, None; Xiaorong Liu, None
  • Footnotes
    Support  NIH Grants R01EY019034 (X.L.), R01EY01995 (H.F.Z.), William & Mary Greve Special Scholar Award from the Research to Prevent Blindness (X.L.), Northwestern Memorial Foundation / Brinson Foundation (X.L.), BrightFocus Foundation (X.L. and L.F.), Mid-west Eye Banks Research Grant (X.L.), and the Illinois Society for the Prevention of Blindness (H.C.).
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2556. doi:
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    • Get Citation

      Liang Feng, Hui Chen, Ji Yi, Hao F Zhang, Xiaorong Liu; Brain-Derived Neurotrophic Factor Protects Retinal Ganglion Cells and Visual Functions in Mice with Long-Term Ocular Hypertension
      . Invest. Ophthalmol. Vis. Sci. 2016;57(12):2556.

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

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Abstract

Purpose : Growing evidences suggest that brain-derived neurotrophic factor (BDNF) plays an important role to preserve vision in eye diseases. In this study we investigated whether BDNF signaling exerts long-term neuroprotective effects on retinal ganglion cell (RGC) survival and visual functions against the chronic intraocular pressure (IOP) elevation.

Methods : A previously established mouse model with chronic IOP elevation (Feng et al., 2013) was adopted when BDNF signaling was manipulated either genetically or pharmacologically. Transgenic mouse line (Thy-1-CreERT2; BDNFstop) to overexpress BDNF (BDNF_OE) in a temporally- and spatially-controlled manner was generated. An agonist for TrkB (high-affinity receptor of BDNF), 7,8-dihydroxyflavone (7,8-DHF), was prepared in mouse drinking water. Full-field electroretinogram (ERG), optical coherence tomography (OCT), mouse optomotor test, and immunohistochemistry were performed to examine the visional functions of retinal morphological changes in different experimental conditions. Various statistical analyses were applied to reveal the differences among experimental groups.

Results : The combined ganglion cell layer (GCL) and neuronal fiber layer (NFL) thickness (GCL + NFL) reduced 44.5% in mice with long-term ocular hypertension, while over-expression of BDNF reduced the decrease of GCL + NFL thickness to 2.9% (p< 0.005). The RGC loss and axon loss were also significantly delayed in BDNF_OE mice. The long-term ocular hypertension induced a gradual decrease of visual acuity (p < 0.001) and inner retinal function (p < 0.001), which were also alleviated by BDNF_OE. Meanwhile over-expression of BDNF compensated the dendritic atrophy in ON-type RGCs (p < 0.005) upon the chronic IOP elevation. Moreover, administration of 7,8-DHF activated the BDNF/TrkB signaling in the retina, resulting in a similar protective effect on RGCs and vision in ocular hypertensive mice.

Conclusions : Our data demonstrated that up-regulation of BDNF/TrkB signaling protects RGC and vision in mice with sustained IOP elevation. These studies provided further supports for developing BDNF-mediated therapeutic intervention to preserve vision in glaucoma.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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