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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)
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.
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.
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).
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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