During the previous grant period, we have investigated the neural basis of the focal dystonia, benign essential blepharospasm (BEB). Our studies reveal that the spasms of lid closure characteristic of this disorder are an exaggeration of the abnormal blinks that occur with dry eye. With dry eye, a single stimulus evokes an abnormal series of repetitive blinks, blink oscillations. In addition to lid spasms, BEB patients also experience photophobia, an abnormal sensitivity to light. Similar to BEB patients, individuals with dry eye and migraine also have blink oscillations and photophobia. We hypothesize that trigeminal sensitization; an increased excitability of the trigeminal system produces blink oscillations and underlies photophobia in all three disorders. The overall goal of this proposal is to determine how trigeminal sensitization produces the same symptoms in these three disorders despite their very different etiology. We propose four specific aims to accomplish these goals: 1) Determine the cellular mechanisms of trigeminal sensitization and how this neural modification produces blink oscillations; 2) Identify how the cerebellum converts blink oscillations into spasms of lid closure in BEB; 3) Test our novel model for the neural basis of photophobia and assess the contribution of different neural mechanisms to photophobia; and 4) Establish the role of trigeminal sensitization such as occurs with dry eye in modifying the neural circuit that generates tears and blinking. The proposed studies will elucidate the neural bases of spasms of lid closure and photophobia, symptoms that can cause functional blindness. The results of these investigations may point to future treatment options for symptoms that plague individuals with BEB, dry eye and migraine. ? ? ?
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