Research Summary

My clinical practice is focused on pediatric ophthalmology and neuro-ophthalmology. Through clinical research, my goal is to find better methods to diagnose and treat the diseases which affect my patients. Often, my laboratory research is inspired and guided by the patients that I encounter with visual problems in my office.

In the laboratory, I am studying the organization and function of the central visual system in primates. I am presently the principal investigator of a study entitled "Structural Basis of Amblyopia and Strabismus" supported by the National Eye Institute. My ultimate goal is to explain how visual perception occurs in the human brain. To pursue this objective, we conduct experiments in normal, amblyopic, and strabismic primates. Research on amblyopic and strabismic subjects is important, for two reasons. First, amblyopia causes visual impairment in about 2% of the American population. Strabismus is even more common, and often leads to amblyopia and loss of stereovision. Research upon these diseases therefore has important practical implications for the prevention of visual loss and the protection of public health. Second, research on amblyopia and strabismus can provide insight into the normal function of the visual system. In strabismus and amblyopia, visual function becomes impaired early in life, yet the visual pathway suffers no destructive physical lesion. If one can determine exactly which cells and connections have been disrupted by abnormal sensory experience in subjects with amblyopia or strabismus, one will presumably have discovered properties and pathways vital for normal perception.

The purpose of the human visual system is to provide a supremely efficient means for the rapid assimilation of information from the environment to guide behavior. The retina serves as a peripheral transducer, by converting images of light into patterns of electrical signals. These signals are conducted along the primary optic pathway to a relay nucleus in the thalamus, called the lateral geniculate body. Virtually the entire output of the lateral geniculate body is relayed to the primary visual cortex. Within the primary visual cortex, visual information is processed by cells arranged within an elaborate system comprised of overlapping vertical columns and horizontal layers. Our first objective is to map the functional architecture of the primary visual cortex, to understand how groups of cells are organized in a modular fashion for information analysis. We are using autoradiography, axon tracing, cytochrome oxidase histochemistry, functional gene expression, and electrophysiology to accomplish this aim.

After initial processing by the primary visual cortex, images are transferred to several dozen extrastriate visual areas, where perception takes place. It is unclear why the primate brain has so many different visual areas beyond the primary visual cortex. One theory suggests that various cortical areas are specialized for processing different aspects of vision, e.g., motion, color, form, etc. Our second objective is to map the boundaries, layout, topography, and modular architecture of visual regions in extrastriate cortex, to determine how they contribute to visual perception. At present, our attention is focussed upon areas V2, V3, VP, V3A, V4, and V5, which are situated close to V1.

Amblyopia is a disease of the cortex caused by visual deprivation. The most severe form occurs in a child who grows up with a dense unilateral cataract. Even after removal of the cataract, vision remains poor because of projections serving the amblyopic eye within the brain are miswired. Our third objective is to delineate the critical periods for normal development and plasticity of the visual cortex, and to understand how the circuitry and function of the visual cortex are disrupted by visual deprivation and strabismus.

We use the macaque for most of our research, because it provides an excellent model for visual processing in the human brain. In addition, whenever possible, we conduct parallel anatomical studies in human visual cortex. Our fourth objective is to extend and confirm many of our findings in humans. This approach gives us confidence that our animal experiments are yielding valid insights into the development and function of the human visual cortex.