Differences in gene expression between strabismic and normal human extraocular muscles.
OBJECTIVE
Strabismic extraocular muscles (EOMs) differ from normal EOMs in structural and functional properties, but the gene expression profile of these two types of EOM has not been examined. Differences in gene expression may inform about causes and effects of the strabismic condition in humans.


METHODS
EOM samples were obtained during corrective surgery from patients with horizontal strabismus and from deceased organ donors with normal EOMs. Microarrays and quantitative PCR identified significantly up- and down-regulated genes in EOM samples. Analysis was performed on probe sets with more than 3-fold differential expression between normal and strabismic samples, with an adjusted P value of ≤ 0.05.


RESULTS
Microarray analysis showed that 604 genes in these samples had significantly different expression. Expression predominantly was upregulated in genes involved in extracellular matrix structure, and down-regulated in genes related to contractility. Expression of genes associated with signaling, calcium handling, mitochondria function and biogenesis, and energy homeostasis also was significantly different between normal and strabismic EOM. Skeletal muscle PCR array identified 22 (25%) of 87 muscle-specific genes that were significantly down-regulated in strabismic EOMs; none was significantly upregulated.


CONCLUSIONS
Differences in gene expression between strabismic and normal human EOMs point to a relevant contribution of the peripheral oculomotor system to the strabismic condition. Decreases in expression of contractility genes and increases of extracellular matrix-associated genes indicate imbalances in EOM structure. We conclude that gene regulation of proteins fundamental to contractile mechanics and extracellular matrix structure is involved in pathogenesis and/or consequences of strabismus, suggesting potential novel therapeutic targets.
Department of Physiology & Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA.
Amy L
AL
Altick
Cheng-Yuan
CY
Feng
Karen
K
Schlauch
L Alan
LA
Johnson
Christopher S
CS
von Bartheld
D000293:Adolescent; D000328:Adult; D002648:Child; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009801:Oculomotor Muscles / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013285:Strabismus / Q000235:genetics*; D055815:Young Adult
D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger