PMID- 29408880 OWN - NLM STAT- MEDLINE DCOM- 20180402 LR - 20190610 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 13 IP - 2 DP - 2018 TI - Daily visual stimulation in the critical period enhances multiple aspects of vision through BDNF-mediated pathways in the mouse retina. PG - e0192435 LID - 10.1371/journal.pone.0192435 [doi] LID - e0192435 AB - Visual experience during the critical period modulates visual development such that deprivation causes visual impairments while stimulation induces enhancements. This study aimed to determine whether visual stimulation in the form of daily optomotor response (OMR) testing during the mouse critical period (1) improves aspects of visual function, (2) involves retinal mechanisms and (3) is mediated by brain derived neurotrophic factor (BDNF) and dopamine (DA) signaling pathways. We tested spatial frequency thresholds in C57BL/6J mice daily from postnatal days 16 to 23 (P16 to P23) using OMR testing. Daily OMR-treated mice were compared to littermate controls that were placed in the OMR chamber without moving gratings. Contrast sensitivity thresholds, electroretinograms (ERGs), visual evoked potentials, and pattern ERGs were acquired at P21. To determine the role of BDNF signaling, a TrkB receptor antagonist (ANA-12) was systemically injected 2 hours prior to OMR testing in another cohort of mice. BDNF immunohistochemistry was performed on retina and brain sections. Retinal DA levels were measured using high-performance liquid chromatography. Daily OMR testing enhanced spatial frequency thresholds and contrast sensitivity compared to controls. OMR-treated mice also had improved rod-driven ERG oscillatory potential response times, greater BDNF immunoreactivity in the retinal ganglion cell layer, and increased retinal DA content compared to controls. VEPs and pattern ERGs were unchanged. Systemic delivery of ANA-12 attenuated OMR-induced visual enhancements. Daily OMR testing during the critical period leads to general visual function improvements accompanied by increased DA and BDNF in the retina, with this process being requisitely mediated by TrkB activation. These results suggest that novel combination therapies involving visual stimulation and using both behavioral and molecular approaches may benefit degenerative retinal diseases or amblyopia. FAU - Mui, Amanda M AU - Mui AM AD - Department of Ophthalmology, Emory University, Atlanta, GA, United States of America. AD - Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA, United States of America. FAU - Yang, Victoria AU - Yang V AD - Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA, United States of America. AD - Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, United States of America. FAU - Aung, Moe H AU - Aung MH AD - Neuroscience Program, Emory University, Atlanta, GA, United States of America. FAU - Fu, Jieming AU - Fu J AD - Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA, United States of America. AD - Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, United States of America. FAU - Adekunle, Adewumi N AU - Adekunle AN AD - Department of Ophthalmology, Emory University, Atlanta, GA, United States of America. AD - Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA, United States of America. FAU - Prall, Brian C AU - Prall BC AD - Department of Ophthalmology, Emory University, Atlanta, GA, United States of America. AD - Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA, United States of America. AD - Neuroscience Program, Emory University, Atlanta, GA, United States of America. FAU - Sidhu, Curran S AU - Sidhu CS AD - Department of Ophthalmology, Emory University, Atlanta, GA, United States of America. FAU - Park, Han Na AU - Park HN AD - Department of Ophthalmology, Emory University, Atlanta, GA, United States of America. AD - Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA, United States of America. FAU - Boatright, Jeffrey H AU - Boatright JH AD - Department of Ophthalmology, Emory University, Atlanta, GA, United States of America. AD - Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA, United States of America. FAU - Iuvone, P Michael AU - Iuvone PM AD - Department of Ophthalmology, Emory University, Atlanta, GA, United States of America. AD - Neuroscience Program, Emory University, Atlanta, GA, United States of America. AD - Department of Pharmacology, Emory University, Atlanta, GA, United States of America. FAU - Pardue, Machelle T AU - Pardue MT AUID- ORCID: 0000-0001-8738-6839 AD - Department of Ophthalmology, Emory University, Atlanta, GA, United States of America. AD - Neuroscience Program, Emory University, Atlanta, GA, United States of America. AD - Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA, United States of America. AD - Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, United States of America. LA - eng GR - R01 EY004864/EY/NEI NIH HHS/United States GR - P30 EY006360/EY/NEI NIH HHS/United States GR - R01 EY014026/EY/NEI NIH HHS/United States GR - R01 EY021592/EY/NEI NIH HHS/United States GR - R01 EY016435/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180206 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Brain-Derived Neurotrophic Factor) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Chromatography, High Pressure Liquid MH - Contrast Sensitivity MH - Dopamine/metabolism MH - Electroretinography MH - Evoked Potentials, Visual MH - Mice MH - Mice, Inbred C57BL MH - *Photic Stimulation MH - Retina/*metabolism MH - Signal Transduction MH - *Visual Acuity PMC - PMC5800661 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2018/02/07 06:00 MHDA- 2018/04/03 06:00 PMCR- 2018/02/06 CRDT- 2018/02/07 06:00 PHST- 2017/08/09 00:00 [received] PHST- 2018/01/22 00:00 [accepted] PHST- 2018/02/07 06:00 [entrez] PHST- 2018/02/07 06:00 [pubmed] PHST- 2018/04/03 06:00 [medline] PHST- 2018/02/06 00:00 [pmc-release] AID - PONE-D-17-29568 [pii] AID - 10.1371/journal.pone.0192435 [doi] PST - epublish SO - PLoS One. 2018 Feb 6;13(2):e0192435. doi: 10.1371/journal.pone.0192435. eCollection 2018.