New avenues for the treatment of amblyopia

Aug 13 2007

Contrary to accepted dogma, a University of Maryland researcher has developed a method that allows an adult to recover function in an eye that has been damaged and dysfunctional throughout life.

In a paper in the August 12 issue of Nature Neuroscience, Elizabeth Quinlan, associate professor of biology at the University of Maryland, and members of her research team, show that complete visual deprivation promotes subsequent recovery in an eye that has had severely compromised vision from birth to adulthood. It is the first demonstration that visual experience can regulate the recovery of function in amblyopic adults.

The finding may open new avenues for the treatment of amblyopia, a disorder of the eye characterized by poor vision in an eye that is otherwise physically normal. Amblyopia is estimated to affect between one and five percent of the world's population.

The research also demonstrates that synaptic plasticity, the ability of synaptic contacts between neurons to be strengthened or weakened in response to specific patterns of activity, can be reversibly regulated by experience throughout lifetime.

The research was performed in the Quinlan lab by graduate student Hai-Yan He, postdoctoral fellow Baishali Ray, and undergraduate Katie Dennis.

Early in postnatal life, the brains of all animals, including humans, possess a heightened sensitivity to environmental stimuli. Such postnatal sensory experience sculpts the connections between neurons and allows the proper development of sensory and motor function.

For example, visual experience in early postnatal life is required for the proper maturation of the visual system. An injury in either eye early in development will significantly compromise the development of normal vision.

In fact, if a child is born with a cataract in one eye, or any of a number of other restrictions that make the input into the two eyes unequal, amblyopia will develop. In amblyopia, the brain learns to ignore input from the weak or damaged eye and respond only to signals coming in from the strong eye.

The asymmetry impairs the development of three-dimensional vision, and vision in the compromised eye can deteriorate to the point of blindness. It previously has been demonstrated repeatedly that amblyopia can be reversed only if the damaged eye is repaired early in postnatal life.

Clinical studies demonstrate that the probability of recovery of function in amblyopia caused by unilateral cataract depends on the age at which the cataract is removed. The probability of full recovery is highest when the cataract is removed during the first three years of life.

“That is consistent with a large body of evidence that the juvenile mammalian cortex is more ‘plastic' than that of adults,” said Quinlan, “and can reorganize synaptic connections more easily in response to manipulations of sensory and motor experience.”

Using a rodent model system, Quinlan's team mimicked the presence of a unilateral cataract by blocking the input into one eye from eye-opening to adulthood. Much as a cataract does, the experimental occlusion caused rapid deterioration in the acuity of the deprived eye.

It has been previously established that normal visual function in the occluded eye cannot be recovered if the occlusion was removed in adulthood. “However, when we placed the subjects into a light-tight dark room for a period of complete visual deprivation prior to removing the occlusion, we were able to produce a rapid recovery of visual acuity after removal of the occlusion” said Hai-Yan He, the first author of the paper.

“Dark exposure drives down the strength of the synapses serving the two eyes, restoring the symmetry that was previously lacking in the amblyopic adult,”Quinlan said.

“The decrease in synaptic strength combined with the restoration of symmetry may allow the visual cortex to be more plastic and respond to changes in subsequent visual input.”

The Quinlan lab also has evidence at the molecular level that following dark exposure, the adult visual cortex looks more like that of an immature visual cortex. “Visual deprivation turns back the clock on the visual cortex, returning it to a more plastic, juvenile-like state, said Quinlan.

Quinlan and her team propose that such a non-invasive method to reverse the effects of amblyopia has important therapeutic potential. “The non-invasive nature of dark exposure is particularly well-suited to work in combination with current behavioral therapy to improve treatment success for human amblyopia,” Quinlan said.