The exquisite precision with which the eyes acquire, pursue and fixate visual targets appears to stand in contrast to the more gross methods used to correct abnormalities in the system. Extraocular muscles (EOMs) may be surgically shortened or repositioned to compensate for inappropriate motor activity. Botulinum toxin type A can be injected in order to weaken a particular muscle so that it may perform better in relation to other muscles, although force changes after such injections have not been systematically studied. The predicted outcome of these measures can be unreliable and the interventions may need to be repeated in the same patient because it's often difficult to obtain the proper alignment of the eyes with a single procedure. While the clinical effectiveness of these strategies is unquestioned, there is obvious need to improve their precision and predictability. This proposal, using cats and monkeys, will primarily focus on two related aspects of eye movement control exposed by perturbing the normal system. I) How does EOM contractile force change from O-2 months post botulinum toxin injection and do those changes directly relate to eye displacement changes? 2) How precise are motoneuron MN firing patterns during repeated identical movements and how might that precision be altered after botulinum toxin injection? Additionally, is there a relationship between VIth nerve branching and orbital and global layer of the lateral rectus muscle? Studies of EOM electromyography (EMG), muscle immuno-histochemistry and myosin expression will be carried out concurrently with the examination of these questions. The correlative evaluation of MN firing, whole muscle plus motor unit force, muscle cytology and EMG measures with eye displacement is unique and unavailable in either normal or botulinum toxin treated motor systems. It is hoped that these studies will provide information critical to clinicians seeking to improve patient outcomes as well as basic researchers who want to understand the complex dynamics of eye movements.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY011249-07
Application #
6524919
Study Section
Visual Sciences B Study Section (VISB)
Program Officer
Hunter, Chyren
Project Start
1995-12-06
Project End
2005-07-31
Budget Start
2002-08-01
Budget End
2005-07-31
Support Year
7
Fiscal Year
2002
Total Cost
$250,600
Indirect Cost
Name
Virginia Commonwealth University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298
Dimitrova, Diana M; Allman, Brian L; Shall, Mary S et al. (2009) Polyneuronal innervation of single muscle fibers in cat eye muscle: inferior oblique. J Neurophysiol 101:2815-21
Bishop, Keith N; McClung, J Ross; Goldberg, Stephen J et al. (2007) Anatomic and physiological characteristics of the ferret lateral rectus muscle and abducens nucleus. J Appl Physiol 103:1706-14
McClung, J Ross; Allman, Brian L; Dimitrova, Diana M et al. (2006) Extraocular connective tissues: a role in human eye movements? Invest Ophthalmol Vis Sci 47:202-5
Sklavos, S; Dimitrova, D M; Goldberg, S J et al. (2006) Long time-constant behavior of the oculomotor plant in barbiturate-anesthetized primate. J Neurophysiol 95:774-82
Shall, Mary S; Van Cleave, Susan; Dimitrova, Diana M et al. (2005) Lateral rectus muscle changes after bilateral neonatal labyrinthectomy in the ferret. J Vestib Res 15:243-51
McClung, J R; Cullen, K E; Shall, M S et al. (2004) Effects of electrode penetrations into the abducens nucleus of the monkey: eye movement recordings and histopathological evaluation of the nuclei and lateral rectus muscles. Exp Brain Res 158:180-8
Dimitrova, Diana M; Shall, Mary S; Goldberg, Stephen J (2003) Stimulation-evoked eye movements with and without the lateral rectus muscle pulley. J Neurophysiol 90:3809-15
Shall, Mary S; Dimitrova, Diana M; Goldberg, Stephen J (2003) Extraocular motor unit and whole-muscle contractile properties in the squirrel monkey. Summation of forces and fiber morphology. Exp Brain Res 151:338-45
Dimitrova, Diana M; Shall, Mary S; Goldberg, Stephen J (2002) Short-term effects of botulinum toxin on the lateral rectus muscle of the cat. Exp Brain Res 147:449-55
McClung, J R; Shall, M S; Goldberg, S J (2001) Motoneurons of the lateral and medial rectus extraocular muscles in squirrel monkey and cat. Cells Tissues Organs 168:220-7

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