June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
BDNF mediates the protective effects of exercise in the diabetic rat retina
Author Affiliations & Notes
  • Rachael S Allen
    Ophthalmology, Emory University School of Med, Atlanta, GA
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA
  • Adam Hanif
    Ophthalmology, Emory University School of Med, Atlanta, GA
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA
  • Marissa Ann Gogniat
    Ophthalmology, Emory University School of Med, Atlanta, GA
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA
  • Brian Prall
    Ophthalmology, Emory University School of Med, Atlanta, GA
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA
  • Moe Hein Aung
    Ophthalmology, Emory University School of Med, Atlanta, GA
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA
  • Megan Prunty
    Ophthalmology, Emory University School of Med, Atlanta, GA
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA
  • Lukas Mees
    Ophthalmology, Emory University School of Med, Atlanta, GA
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA
  • P Michael Iuvone
    Ophthalmology, Emory University School of Med, Atlanta, GA
    Pharmacology, Emory University School of Med, Atlanta, GA
  • Machelle T Pardue
    Ophthalmology, Emory University School of Med, Atlanta, GA
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA
  • Footnotes
    Commercial Relationships Rachael Allen, None; Adam Hanif, None; Marissa Gogniat, None; Brian Prall, None; Moe Aung, None; Megan Prunty, None; Lukas Mees, None; P Iuvone, None; Machelle Pardue, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 5184. doi:
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      Rachael S Allen, Adam Hanif, Marissa Ann Gogniat, Brian Prall, Moe Hein Aung, Megan Prunty, Lukas Mees, P Michael Iuvone, Machelle T Pardue; BDNF mediates the protective effects of exercise in the diabetic rat retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5184.

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

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Abstract

Purpose: Exercise has been shown to be neuroprotective and neuroregenerative in a variety of neural tissues. Previously, we showed that exercise reduced retinal function deficits and photoreceptor cell death in a light-induced retinal degeneration model while increasing retinal levels of BDNF (Lawson et al. J Neurosci 2014). Treating exercised mice with ANA-12, a TrkB BDNF receptor antagonist, reduced this protection. We hypothesize that BDNF mediates the protective effects of exercise in the diabetic retina.

Methods: Long Evans rats were assigned to one of four diabetic (DM) groups (n = 4-8) (active + vehicle, inactive + vehicle, active + ANA-12, or inactive + ANA-12) or an inactive, non-diabetic control group. Hyperglycemia was induced using the streptozotocin (STZ; 100 mg/kg) model of Type 1 diabetes with glucose levels >250 mg/dL considered diabetic. Rats were given treadmill training 5 days/week for 30 min at a speed of 0 m/min (inactive) or 15m/min (active) for 8 weeks. ANA-12 or vehicle solution was injected 2.5 h prior to exercise. Contrast sensitivity was assessed every two weeks using an optokinetic tracking system. Retinal function was assessed at 4 and 8 weeks post-STZ using electroretinogram.

Results: Contrast sensitivity was significantly reduced in DM inactive + vehicle rats versus controls at 8 weeks post-STZ (DM inactive + vehicle: 3.52 ± 0.16%; Control: 10.05 ± 0.90%; p < 0.001). Exercise significantly preserved contrast sensitivity in DM active + vehicle rats compared with inactive + vehicle (p < 0.01), and this protection was significantly eliminated in ANA-12 treated rats (active + vehicle: 5.23 ± 0.30%; ANA-12 + active: 4.08 ± 0.25%; ANA-12 + inactive: 3.95 ± 0.13%; p < 0.01). Flicker ERG implicit times were significantly delayed in DM inactive + vehicle rats compared with controls (DM inactive + vehicle: 223.75 ± 1.81 ms; Control: 215 ± 1.18 ms; p < 0.004). Exercise significantly reduced these delays (p < 0.003), and ANA-12 significantly eliminated this effect (p < 0.02; active + vehicle: 217.07 ± 0.98 ms; ANA-12 + active 222.67 ± 2.45 ms; ANA-12 + inactive: 221.5 ± 1.76 ms).

Conclusions: Exercise is neuroprotective against early visual dysfunction in diabetic rats. ANA-12 treatment reduced this protection, suggesting a BDNF-mediated signaling mechanism. Exercise may prove to be a promising treatment to reduce early retinal defects in diabetes.

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