Extraocular muscle differs from other skeletal muscle in physiological characteristics and susceptability to neuromuscular disorders. Nitric oxide is a ubiquitous cell signaling molecule which modulates skeletal muscle contraction and neuromuscular transmission. We hypothesize that NO plays similar roles in extraocular muscle, and nitric oxide systems may be important in explaining extraocular muscle's resistence to degeneration by Duchenne muscular dystrophy. Further, modulation of neuromuscular transmission by nitric oxide drugs may be useful in treatment of myasthenia gravis, a disorder which preferentially affects extraocular muscle. To evaluate these hypotheses, we will characterize in extraocular muscle protein levels, enzymatic activities, and anatomic localization of nitric oxide synthase, the enzyme which generates nitric oxide. The effect of nitric oxide donors and nitric oxide synthase inhibitors on contractile function and evoked and miniature endplate potentials of extraocular and control muscles will be determined. After nitric oxide's functions in normal EOM are determined, the ability of nitric oxide modulators to reverse the neuromuscular transmission block of myasthenia gravis will be assessed. From dystrophin-deficient mice, nitric oxide synthase activity and effect of NO modulating drugs on contractile characteristics of extraocular muscle will be evaluated. In addition to the significance for treatment of Duchenne muscular dystrophy and myasthenia gravis, the results of these investigations will be important for other disorders of extraocular muscle, such as strabismus, genetic ocular motility disorders, congenital myasthenic syndromes, and blepharospasm.
| Kaminski, Henry J; Richmonds, Chelliah R; Kusner, Linda L et al. (2002) Differential susceptibility of the ocular motor system to disease. Ann N Y Acad Sci 956:42-54 |
| Porter, John D; Khanna, Sangeeta; Kaminski, Henry J et al. (2002) A chronic inflammatory response dominates the skeletal muscle molecular signature in dystrophin-deficient mdx mice. Hum Mol Genet 11:263-72 |
| Kaminski, Henry J; Richmonds, Chelliah R (2002) Nitric oxide and cGMP modulation of extraocular muscle contraction. Ann N Y Acad Sci 956:399-400 |
| Kaminski, Henry J; Richmonds, Chelliah R (2002) Extraocular muscle fatigue. Ann N Y Acad Sci 956:397-8 |
| Richmonds, C R; Kaminski, H J (2001) Nitric oxide synthase expression and effects of nitric oxide modulation on contractility of rat extraocular muscle. FASEB J 15:1764-70 |
| Porter, J D; Khanna, S; Kaminski, H J et al. (2001) Extraocular muscle is defined by a fundamentally distinct gene expression profile. Proc Natl Acad Sci U S A 98:12062-7 |
| Kaminski, H J; Andrade, F H (2001) Nitric oxide: biologic effects on muscle and role in muscle diseases. Neuromuscul Disord 11:517-24 |
| Andrade, F H; Porter, J D; Kaminski, H J (2000) Eye muscle sparing by the muscular dystrophies: lessons to be learned? Microsc Res Tech 48:192-203 |
| Richmonds, C R; Kaminski, H J (2000) Nitric oxide myotoxicity is age related. Mech Ageing Dev 113:183-91 |
| Kaminski, H J; Daroff, R B (2000) Treatment of ocular myasthenia: steroids only when compelled. Arch Neurol 57:752-3 |
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