Effects of elevated thyroid hormone on adult rabbit extraocular muscles.
OBJECTIVE
Human extraocular muscles (EOM) are preferentially susceptible to thyroid eye disease. Although the specific cause of this autoimmune disorder is unknown, it is often associated with elevated thyroid hormone levels. Thus, the effect of elevated thyroid hormone levels on cross-sectional area, myofiber size, satellite cells, and myosin heavy chain (MyHC) isoform expression was examined in adult rabbit EOMs, to determine how elevated thyroid hormone alters EOM biology.


METHODS
After 1 month of elevated thyroid hormone levels, the EOMs were removed and prepared for histologic examination. Total muscle mass, myofiber size, patterns of MyHC isoform expression, and the number of satellite cells were determined.


RESULTS
Elevated thyroid hormone levels significantly decreased muscle mass, total number of myofibers, and mean cross-sectional area of the myofibers. Alterations in MyHC isoform expression were extremely complex, but several basic patterns emerged. The percentages of neonatal- and developmental-positive myofibers decreased in almost all EOM regions examined, and the percentages of slow-positive myofibers significantly increased. In contrast to normal EOMs, which retain a population of activated satellite cells throughout life, elevated thyroid hormone levels resulted in the virtual disappearance of MyoD-positive cells and a decrease in Pax7-positive cells.


CONCLUSIONS
The reductions in EOM size, number of fibers expressing developmental and neonatal MyHC, and number of MyoD- and Pax7-positive satellite cells suggest that elevated thyroid hormone levels decrease the ongoing myofiber remodeling normally seen in the EOM. These catabolic changes have important implications for maintenance of function in the EOMs.
Harrison
Andrew R
AR
Department of Ophthalmology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Lee
Michael S
MS
McLoon
Linda K
LK
D000818:Animals; D006980:Hyperthyroidism / Q000139:chemically induced / Q000503:physiopathology*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology*; D017570:MyoD Protein / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism*; D009801:Oculomotor Muscles / Q000378:metabolism / Q000503:physiopathology*; D051763:PAX7 Transcription Factor / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D011817:Rabbits; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism / Q000473:pathology*; D014285:Triiodothyronine, Reverse / Q000633:toxicity
D017570:MyoD Protein; D051763:PAX7 Transcription Factor; D020033:Protein Isoforms; D014285:Triiodothyronine, Reverse; D018995:Myosin Heavy Chains