# Exploiting principles of timing-dependent synaptic plasticity to treat amblyopia

> **NIH NIH K08** · BOSTON CHILDREN'S HOSPITAL · 2021 · $239,256

## Abstract

This proposal describes a 5-year training program for the development of an academic career focused
on improving therapy for amblyopia by advancing our understanding and exploitation of synaptic plasticity
mechanisms. My graduate training in electrophysiology and synaptic plasticity carried through during my
ophthalmology residency and neuro-ophthalmology fellowship at Massachusetts Eye and Ear Infirmary (MEEI)
and Harvard Medical School (HMS). During this time, I have been working in the laboratory of Dr. Mark Bear at
the nearby Massachusetts Institute of Technology (MIT) gathering early data on a potential new therapeutic
approach for amblyopia. This work will continue during my pediatric ophthalmology fellowship at Boston
Children’s Hospital (BCH) through July 2019. I wish to continue this research and my development to prepare
for an independent research career. My long-term goals include making major contributions to the
understanding of the synaptic mechanisms underlying amblyopia while providing translational insights that can
yield new therapeutic approaches for patients with central visual dysfunction. Dr. Bear, a world expert on
amblyopia and synaptic physiology and plasticity with a proven track record of productivity and mentorship, will
serve as mentor. An advisory committee comprised of Drs. David Hunter (BCH/HMS), Ed Boyden (MIT), and
Peter Bex (Northeastern University) will guide my research and career development. This MEEI-sponsored
project will take place in the rich environments of MIT, with access to resources at MEEI, BCH and HMS.
 The proposed research program examines interocular temporal phase offset training (TPOT), which is
predicated on timing-dependent principles of synaptic plasticity, as a potential new therapeutic approach to
amblyopia while elucidating properties of signal integration in visual cortex. In our initial experiments, we show
that TPOT is sufficient to selectively strengthen visually evoked potentials in the inherently weaker ipsilateral
eye and shift ocular dominance in mice. In the first Aim, I will characterize the properties of TPOT, including
stimulus selectivity, optimal parameters for efficacy and age limits. I will define the interaction of signal phase
with contrast reduction, which has been used to treat amblyopia, and determine the cortical laminar-specific
effects of TPOT. The second Aim is to gain mechanistic insights into the TPOT effect. I will learn and apply 2-
photon calcium imaging techniques to define the ocular dominance shift at the neuronal level, and selectively
target NMDA receptor expression in the visual cortex to uncover their role in TPOT-induced visual cortical
plasticity. The third Aim will apply TPOT to monocularly deprived mice, a widely studied animal model for
amblyopia, with the goals of promoting visual recovery and generalizing the TPOT effect. In conducting these
experiments, I will gain considerable experience with advanced techniques to study murine visual physi...

## Key facts

- **NIH application ID:** 10222702
- **Project number:** 5K08EY030164-03
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Eric Dean Gaier
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $239,256
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10222702

## Citation

> US National Institutes of Health, RePORTER application 10222702, Exploiting principles of timing-dependent synaptic plasticity to treat amblyopia (5K08EY030164-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10222702. Licensed CC0.

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