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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY007391-23
Application #
8123312
Study Section
Central Visual Processing Study Section (CVP)
Program Officer
Araj, Houmam H
Project Start
1987-09-30
Project End
2014-08-31
Budget Start
2011-09-01
Budget End
2014-08-31
Support Year
23
Fiscal Year
2011
Total Cost
$368,357
Indirect Cost
Name
State University New York Stony Brook
Department
Neurosciences
Type
Schools of Medicine
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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