This proposal tests a model developed in our laboratory that explains the development of benign essential blepharospasm (BEB). BEB is a focal dystonia of basal ganglia origin, characterized by uncontrollable spasms of lid closure. BEB typically emerges in people over 50 years old with patients initially complaining of dry eyes and excessive blinking. Our model postulates that a combination of two factors causes BEB. First, a subclinical loss of dopamine cells in the basal ganglia producing an increase in reflex blink excitability plays a permissive role in the growth of BEB. Second, the development of dry eye or a weakening of the lid closing, orbicularis oculi (00) muscle is the proximal cause of BEB. The permissive action of the basal ganglia on trigeminal reflex blink circuits allows the increase in reflex blink excitability associated with """"""""dry eye"""""""" or 00 weakness to evolve into spasms of lid closure. The application proposes rigorous tests of our model. First, a recreation of the permissive and proximal factors postulated to cause BEB in humans will be produced in rodents to create an animal model of BEB. With this animal model of BEB, treatment procedures designed to prevent the development of BEB will be tested. Second, the changes in reflex blink excitability that occur with dry eye and 00 weakening will be fully investigated in normal human and rodents. Third, the role of age in the development of BEB will be investigated in normal human and rodents. Fourth, we will investigate the cellular changes in rodent trigeminal reflex blink circuits that occur with BEB, dopamine cell loss and 00 muscle weakness. The approach of combining human and animal studies allows a continuous comparison of human and animal results so that the data acquired about the cellular and physiological changes caused by BEB in animal will yield valuable knowledge about BEB in humans.
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