Amblyopia typically is treated by patching the fellow eye to strengthen the affected eye with the goal of restoring normal eye dominance. If correction is not achieved prior to the closing of a “critical period” that ends in early adolescence, visual impairments are more difficult to treat, if not permanent.

Research published today, led by Aaron W. McGee, PhD, assistant professor in the University of Louisville Department of Anatomical Sciences and Neurobiology, may lead to changes in how amblyopia is treated, particularly in adults. The research shows that eye dominance and visual acuity are controlled by different areas of the brain, and that one can be corrected without correcting the other.

“We unexpectedly discovered that they aren’t related. They’re independent,” McGee said. “It may not be necessary to instill normal eye dominance to correct visual acuity.”

Previously, McGee and fellow researchers identified a gene called ngr1 as essential in closing the critical period. He found that deleting ngr1 in animal models permits the critical period to remain open or to re-open, facilitating recovery of normal eye dominance and visual acuity. However, the relationship between the improved visual acuity and eye dominance was not clear.

Today’s research reports that recovery of eye dominance alone is not sufficient to promote recovery of acuity, and recovery of acuity can occur even if eye dominance remains impaired. McGee and his colleagues found that eye dominance is regulated by the brain’s primary visual cortex, while visual acuity is governed by another area of the brain, the thalamus.

McGee is the senior author on the article, published in Current Biology, (). Co-authors include Céleste-Élise Stephany PhD, a graduate student at the University of Southern California at the time of the research and now a postdoctoral fellow at Harvard Medical School, Shenfeng Qiu, PhD, assistant professor of the University of Arizona, and others.

The researchers applied tools to selectively delete the ngr1 gene in different areas of the brain. When ngr1 was deleted from the primary visual cortex, normal eye dominance was recovered but acuity remained impaired. When ngr1 was deleted from the thalamus, eye dominance was impaired, but visual acuity recovered to normal.

“Genes that are limiting recovery from amblyopia are working in parts of brain circuitry that previously were not recognized to have a role in improving visual acuity,” McGee said. “This could allow researchers to address acuity directly, without having to restore normal eye dominance.”

Established in 2002, the RPB Walt and Lilly Disney Award for Amblyopia Research is intended to stimulate, strengthen and promote research to improve the diagnosis and treatment of amblyopia. The grant is offered to exceptional ophthalmic scientists – MDs or PhDs – with research pursuits of potential significance and promise. McGee is one of two scientists to receive the award in 2016.

“Dr. McGee’s funding from RPB addresses a major cause of blindness in children – namely, amblyopia. The potential to reverse ‘lazy eye’ through medical therapy would be a major advance in curing childhood visual disabilities and improve the quality of life for those affected. His research is exciting and has major potential translational clinical impact,” said Henry Kaplan, MD, chair of the UofL Department of Ophthalmology and Visual Sciences.

Amblyopia occurs in 2 to 3 percent of children and presents with a number of impairments in spatial vision including stereopsis, or depth perception. Permanent visual deficits may result if amblyopia is not treated during a critical period for development of the visual system that ends in early adolescence. The funded research builds on McGee’s previous work investigating how the timing and duration of critical periods in the visual system are determined. McGee will test methods for reversing the loss of depth perception resulting from amblyopia by “re-opening” the critical period in adulthood to enhance the flexibility, or plasticity, of brain circuitry.

“Previously, we discovered that a gene encoding a neuronal receptor is essential for closing the critical period for visual plasticity,” McGee said. “This award from RPB will enable my lab to explore whether neutralizing this receptor will improve depth perception in the murine model of amblyopia.”

McGee moved from the University of Southern California to join the UofL Department of Ophthalmology and Visual Sciences and Department of Anatomical Sciences and Neurobiology in September 2016. The goals of his research program are to identify treatments for low vision and aberrant eye dominance by understanding critical periods for neural plasticity and how experience drives changes in brain function.

The Disney Award for Amblyopia Research is a two-year award to help the awardee pursue promising scientific leads and take opportunities for which other funds are not readily available. RPB is the world’s leading voluntary organization supporting eye research. Since it was founded in 1960, RPB has provided hundreds of millions of dollars to support research into blinding eye diseases by medical institutions throughout the United States.