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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY007391-13
Application #
6125065
Study Section
Visual Sciences B Study Section (VISB)
Program Officer
Hunter, Chyren
Project Start
1987-09-30
Project End
2001-11-30
Budget Start
1999-12-01
Budget End
2000-11-30
Support Year
13
Fiscal Year
2000
Total Cost
$260,021
Indirect Cost
Name
State University New York Stony Brook
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Kaminer, Jaime; Thakur, Pratibha; Evinger, Craig (2015) Effects of subthalamic deep brain stimulation on blink abnormalities of 6-OHDA lesioned rats. J Neurophysiol 113:3038-46
Evinger, Craig (2015) Benign Essential Blepharospasm is a Disorder of Neuroplasticity: Lessons From Animal Models. J Neuroophthalmol 35:374-9
Kaminer, Jaime; Thakur, Pratibha; Evinger, Craig (2014) Frequency matters: beta-band subthalamic nucleus deep-brain stimulation induces Parkinsonian-like blink abnormalities in normal rats. Eur J Neurosci 40:3237-42
Ryan, Michael; Kaminer, Jaime; Enmore, Patricia et al. (2014) Trigeminal high-frequency stimulation produces short- and long-term modification of reflex blink gain. J Neurophysiol 111:888-95
Evinger, Craig (2013) Animal models for investigating benign essential blepharospasm. Curr Neuropharmacol 11:53-8
Powers, Alice S; Basso, Michele A; Evinger, Craig (2013) Blinks slow memory-guided saccades. J Neurophysiol 109:734-41
Dolgonos, Sarah; Ayyala, Haripriya; Evinger, Craig (2011) Light-induced trigeminal sensitization without central visual pathways: another mechanism for photophobia. Invest Ophthalmol Vis Sci 52:7852-8
Kaminer, Jaime; Powers, Alice S; Horn, Kyle G et al. (2011) Characterizing the spontaneous blink generator: an animal model. J Neurosci 31:11256-67
Schade Powers, Alice; Coburn-Litvak, Pamela; Evinger, Craig (2010) Conditioned eyelid movement is not a blink. J Neurophysiol 103:641-7
Lepora, N F; Porrill, J; Yeo, C H et al. (2009) Recruitment in retractor bulbi muscle during eyeblink conditioning: EMG analysis and common-drive model. J Neurophysiol 102:2498-513

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