Daily visual stimulation in the critical period enhances multiple aspects of vision through BDNF-mediated pathways in the mouse retina

• Type of Material: Article
• Authors: Amanda M. Mui, Emory University; Victoria Yang, Atlanta Veterans Affairs Medical Center; Moe H. Aung, Emory University; Jieming Fu Fu, Atlanta Veterans Affairs Medical Center; Adewumi N. Adekunle, Emory University; Brian C. Prall, Emory University; Curran S. Sidhu, Emory University; Han na Park, Emory University; Jeffrey Boatright, Emory University; P Michael Iuvone, Emory University; Machelle Pardue, Emory University
• Language: English
• Date: 2018-02-06
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
• License: Creative Commons Creative Commons CC0 1.0 Universal
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0192435
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 13
• Issue: 2
• Start Page: e0192435
• End Page: e0192435
• Grant/Funding Information: This work was supported by Rehabilitation Research and Development Service at the Department of Veterans Affairs, Research Career Scientist Award to MTP; Research to Prevent Blindness Departmental Award to Emory Ophthalmology; the Katz Foundation to JHB; and NEI R01 EY016435, R01 EY014026, R01 EY004864, and P30 EY006030.
• Keywords: INNER PLEXIFORM LAYER; EXPERIENCE; MICE; SYSTEM; MESSENGER-RNA; ELECTRORETINOGRAM; GANGLION-CELLS; Science & Technology; A-WAVE; Science & Technology - Other Topics; RAT RETINA; NEUROTROPHIC FACTOR; Multidisciplinary Sciences
• Research Categories: Health Sciences, Opthamology; Health Sciences, Pharmacology; Biology, Neuroscience

Abstract

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.