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Amanda Mui, Brian Christopher Prall, Moe Hein Aung, Tracy Obertone, Hanna Park, Jeffrey H Boatright, Machelle T Pardue; Daily optokinetic testing improves contrast sensitivity through BDNF-mediated pathways. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6189.
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© ARVO (1962-2015); The Authors (2016-present)
Daily exposure of rodents to optokinetic tracking (OKT) assessment in early development leads to hypernormal visual acuity thresholds, an effect associated with upregulation of brain derived neurotrophic factor (BDNF) in the retina. In this study, we investigated (1) whether visual benefit after daily OKT was localized in the retina and generalizable to other visual tasks and (2) whether these visual improvements were mediated by BDNF pathway activation.
C57BL/6J mice (n=29) received daily intraperitoneal injections of TrkB receptor antagonist, ANA-12, or vehicle (1% DMSO and 16.5% Cremphor EL) from P16 to P23. At 1.5-2 hours after the injection, mice were placed in an OptoMotry© OKT chamber (CerebralMechanics, Lethbridge, Alberta, Canada) to be stimulated with full OKT testing (stimulated group) or exposed to gray background screens (non-stimulated, control group). Dark and light-adapted electroretinograms (ERGs) were performed on P21 to compare retinal function of these mice (n=13). At P23, contrast sensitivity thresholds (at optimal gradient 0.103 c/d) along with visual acuity of these animals were obtained to assess the potential benefit of OKT exposure to other visual tasks. Immediately following the final testing, mice were sacrificed and eyes enucleated and fixed. Radial sections were labeled with a BDNF antibody and imaged with fluorescent microscopy.
Daily OKT testing resulted in 60% greater visual acuity thresholds (p<0.001) and 300% greater contrast sensitivity (p<0.01) in vehicle-injected, stimulated mice. In ANA-12 injected mice, improvements were diminished with only 20% greater visual acuity thresholds (p<0.01) and 5% greater contrast sensitivity (p<0.05) compared to control vehicle mice. There were no statistical difference between the ANA-12 and the vehicle-injected, non-stimulated control mice. Mean ERG amplitudes were not significantly different among the different treatment types.
Using daily stimulation with OKT to elicit a visual acuity threshold produced enhanced visual acuity levels and also improved contrast sensitivity compared to control mice. These effects were mediated, at least in part, by activation of BDNF pathway in the retina. Since retinal function did not change in stimulated mice, the observed visual benefits may be result of plasticity occurring in higher order visual processing.
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