Submitted on January 30, 2009
Revised on February 25, 2009
Accepted on March 3, 2009
Influence of hyperthyroid conditions on gene expression in the extraocular muscles of rats
Thomas S. Postler1, Murat T. Budak2, Tejvir S Khurana2, and Neal A. Rubinstein2*
1 Harvard Medical School NEPRC
2 University of Pennsylvania
* To whom correspondence should be addressed. E-mail: nrubinst{at}mail.med.upenn.edu.
Extraocular muscles (EOMs) are a highly specialized type of tissue with a wide range of unique properties, including characteristic innervation, development, and structural proteins. Even though EOMs are frequently and prominently affected by thyroid-associated diseases, little is known about the direct effects of thyroid hormone on these muscles. To create a comprehensive profile of changes in gene expression levels in EOMs induced by thyroid hormone, hyperthyroid conditions were simulated by treating adult Sprague-Dawley rats with intraperitoneal injections of the thyroid hormone T3; subsequently, microarray analysis was used to determine changes in mRNA levels in EOMs from T3-treated animals relative to untreated controls. The expression of 468 transcripts was found to be significantly altered, with 466 of these transcripts down-regulated in EOMs from T3-treated animals. The biological processes into which the affected genes could be grouped included Cellular Metabolism, Transport, Biosynthesis, Protein Localization, and Cell Homeostasis. Moreover, fifteen distinct biochemical canonical pathways were represented among the genes with altered transcription levels. Strikingly, myostatin (Gdf8), a potent negative regulator of muscle growth, was found to be strongly down-regulated in EOMs from T3-treated animals. Taken together, these findings suggest that pathological concentrations of thyroid hormone have a unique effect on gene expression in EOMs, which is likely to play a hitherto neglected role in thyroid-associated ophthalmopathies.
