Interocular Phase Delay Shifts Visual Cortical Dominance: a Potential New Therapeutic Approach for Amblyopia

Amblyopia imparts a delay in visually evoked response (VEP) latency (~5 ms/2 Snellen lines) through the affected eye that neutralizes with successful treatment [1, 2]. The delay in signals reaching the visual cortex may actively preclude visual recovery of the affected eye since delay of synaptic activation tends to weaken visual cortical synapses [3]. Along this line, manipulation of interocular stimulus phase could strengthen the amblyopic eye. To this goal, we hypothesized that introduction of an interocular phase delay would induce plasticity in the visual cortex to shift ocular dominance.

Monday, March 5th from 5:45 pm - 6:00 pm Interocular Phase Delay Shifts Visual Cortical Dominance: a Potential New Therapeutic Approach for Amblyopia Eric Gaier1, Daniel Montgomery2, Arnold Heynen2, Mark Bear2 1 Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA, 2Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA Introduction: Amblyopia imparts a delay in visually evoked response (VEP) latency (~5 ms/2 Snellen lines) through the affected eye that neutralizes with successful treatment [1, 2]. The delay in signals reaching the visual cortex may actively preclude visual recovery of the affected eye since delay of synaptic activation tends to weaken visual cortical synapses [3]. Along this line, manipulation of interocular stimulus phase could strengthen the amblyopic eye. To this goal, we hypothesized that introduction of an interocular phase delay would induce plasticity in the visual cortex to shift ocular dominance. Methods: We employed an established model of visual cortical plasticity termed stimulus-selective response plasticity (SRP), in which exposure to inverting sinusoidal grating stimuli presented to a head-fixed mouse on repeated days induces long-term plasticity in binocular V1 [4]. This potentiation is sinusoidal orientation-specific, and multiple orientations can be tested in parallel. We induced SRP over 6 days of conditioning for 3 orientations (10 min each; 10 Hz inversions) run with no interocular delay, a contralateral eye-leading delay (17 ms), and an ipsilateral eye-leading delay. Results: In adolescent mice (P32, N=3), SRP training with no interocular offset induced significant potentiation of contralateral and ipsilateral VEPs (p values<0.042) with no change in ocular dominance. A similar pattern and magnitude of potentiation was observed in the contralateral-leading condition (p values<0.041) without a change in ocular dominance. In the ipsilateral-leading condition, significant potentiation was specific to the ipsilateral eye (p=0.022) with a significant shift in ocular dominance favoring the ipsilateral eye compared to all other conditions (p values<0.023). We found similar results in older animals (P60, N=7). Conclusions: In the current study, interocular phase delay induced cortical plasticity in an eye-specific manner and was sufficient to shift ocular dominance. Future experiments may further support the potential role for manipulation of interocular stimulus phase to treat amblyopia. References: 1. Parisi, V., et al., Electrophysiological detection of delayed postretinal neural conduction in human amblyopia. Invest Ophthalmol Vis Sci, 2010. 51(10): p. 5041-8. 2. Kelly, J.P., et al., Occlusion therapy improves phase-alignment of the cortical response in amblyopia. Vision Res, 2015. 114: p. 142-50. 3. Smith, G.B., A.J. Heynen, and M.F. Bear, Bidirectional synaptic mechanisms of ocular dominance plasticity in visual cortex. Philos Trans R Soc Lond B Biol Sci, 2009. 364(1515): p. 357-67. 4. Cooke, S.F. and M.F. Bear, Stimulus-selective response plasticity in the visual cortex: an assay for the assessment of pathophysiology and treatment of cognitive impairment associated with psychiatric disorders. Biol Psychiatry, 2012. 71(6): p. 487-95. Keywords: Pediatric neuro-ophthalmology, Miscellaneous Financial Disclosures: It should be noted that the current work applies to a provisional patent, of which EDG is the sole inventor. Plans are in place to execute a limited, exclusive license based on this patent for Luminopia (a virtual reality start-up company in Cambridge, MA Grant Support: There is no direct grant support for this project 2018 Annual Meeting | 261