Botulinum A toxin (BTX) paralyzes neuromuscular transmission by blocking release of acetylcholine from nerve terminals. In recent years, small quantities of BTX have been injected into extraocular muscle of strabismic humans to induce corrective changes in ocular alignment. For many patients, the corrective changes in ocular alignment persist long after the direct paralytic effects of BTX have worn off. These findings suggest that peripheral or central adaptive processes, triggered by BTX paralysis, induce ocular alignment. Despite extensive clinical experience with BTX, however, the nature of these processes is obscure. This study will employ a multidisciplinary approach designed to identify and study the character of these adaptations. The study will examine infant and adult animal models of strabismus as well as human patients selected for BTX therapy. Five specific experiments are planned: 1) To measure passive orbital stiffness and hysteresis in adult and infant monkeys. Preliminary studies in our laboratory suggest that orbital stiffness changes are sensitive indicators of structural changes in the globe-muscle system. 2) To create a clinically relevant animal model of strabismus by performing myectomies of a horizontal rectus muscle. This model will be used to study the effects of BTX treatment to relieve or prevent muscle contracture. 3) To analyze binocular eye movement patterns in monkeys after myectomy and/or BTX treatment. 4) To study ultrastructure in paired agonist-antagonist extraocular muscles after BTX treatment. 5) To compare and study eye movements of human patients treated with BTX. Taken together, our findings should provide significant insights into central and peripheral adaptive mechanisms relevant to the development of strabismus, and its treatment by BTX therapy.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY006632-05
Application #
3263093
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1986-08-01
Project End
1993-07-31
Budget Start
1990-08-01
Budget End
1993-07-31
Support Year
5
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627