The studies proposed in this application continue the efforts of the applicants to understand blink behavior in health and disease. Eyelid movements are critical for maintaining visual integrity. Abnormalities of eyelid movement are a cardinal manifestation of many neurologic diseases, but have received surprisingly little intensive study. Proposed studies use the magnetic search coil technique to monitor eyelid movements and established human and subhuman primate models in order to address three specific objectives.
Specific Aim 1 is designed to describe eyelid kinematics in adult human blinks and characterize the conjugacy and habituation responses of the different classes of blinks. While there is clear evidence that multiple control systems contribute to eyelid movements, the theoretical constructs underlying the notion of discrete eyelid movement systems are not well formulated and the metrics of movements generated by each blink subsystem are not yet well characterized. A key objective of these studies is to identify normal, age-related changes in blink and evaluate the hypothesis that normal aging processes predispose individuals to disorders in blink excitability. These studies also serve to generate a normative data base for comparison in subsequent analyses of the pathophysiology of blink.
Specific Aim 2 examines the excitability of blink systems in the blepharospasm patient. Little is known in regard to eyelid kinematics in vision-threatening eyelid motility disorders such as blepharospasm, ptosis, and facial and trigeminal nerve palsy. Understanding the differential response of blink control systems may yield insight into the pathophysiology and treatment of disorders in the excitability and habituation of blinks, including blepharospasm and hemifacial spasm. Stimulus-response properties and blink habituation will be evaluated before and after treatment with botulinum toxin.
Specific Aim 3 uses an alert monkey model to examine the interocular effects of unilateral paresis of lid closure with botulinum toxin or unilateral reduction in orbicularis oculi motoneuron number via retrograde transport of the neurotoxin ricin. As frontal-eyed species, the interocular linkage of human and subhuman primate eyelid movements is tied to binocular vision, but only limited information is available regarding the adaptive mechanisms that maintain the conjugacy of blinks. The proposed studies take advantage of the conjugacy of monkey blinks in order to better understand the role of adaptive mechanisms in the neural control of blink. Collectively, the short-term goal of these studies is to understand the modality specificity, stimulus-response characteristics, and conjugacy of blink and eyelid movements in health and disease. These data will provide valuable insight into the etiology and treatment of blepharospasm. The long-term goal of the applicants is to utilize human and monkey models to develop and implement improvements in the clinical treatment of a range of eyelid motility disorders.
Showing the most recent 10 out of 11 publications
