Terry J. Smith, M.D.
Research Projects

Our laboratory group is interested in understanding and developing new treatments for Graves' Disease (GD) or thyroid-associated ophthalmopathy (TAO).

Graves’ Disease is an autoimmune process directed primarily at the thyroid. Many of the patients with GD also exhibit inflammation of the tissues around the eye. Orbital manifestations of GD known as TAO, involve the dramatic remodeling of connective tissues surrounding the eye. Alterations in orbital tissue architecture can adversely affect the function and health of the eye in several ways.

• They can deprive the globe of normal irrigation and eyelid coverage, leading to chronic irritation and infection.
• They can compromise the ability of the eyes to move in a coordinated fashion, restricting motility, and resulting in disconjugate gaze and diplopia.
• They can cause cosmetic changes that sometimes exert a profoundly deleterious impact on the psychological health of afflicted patients.
• They can threaten eye sight by compressing the neuro-vascular supply to the eye.

There are no specific safe and effective therapies for TAO. Our overall goal is to identify the molecular and cellular mechanisms responsible for the pathogenesis of orbital involvement in TAO. We have found that patients with TAO have dramatically increased numbers of circulating fibrocytes. These fibrocytes derive from stem cells originating in the bone marrow. They infiltrate the connective tissues of the orbit. We believe that the phenotypic attributes of orbital fibroblasts underlie the propensity of the tissues surrounding the eye to become involved in GD. As a direct consequence of identifying the peculiarities exhibited by these cells, we are now in a strong position to create strategies for interrupting the disease process at a very early stage.

Our work is focused on defining the molecular targets that will lead to effective and specific therapy design.