Craniofacial Muscles

3 Extraocular Muscle Structure and Function
45
to fuse into existing myo fi bers (McLoon and Wirtschafter 2002 ; McLoon et al.
2004 ) . This same process occurs in laryngeal muscles (Goding et al. 2005 ) , suggesting
that this may be a general feature of craniofacial muscles.
The rami fi cations of the continual turnover of myonuclei in single EOM myo fi bers
are unclear. It is has been known for a long time that the EOM are resistant to injury
and often react differently to various intramuscular drug treatments when compared
to limb skeletal muscle. Botulinum toxin A, which in limb skeletal muscles causes
muscle atrophy, results in no long-term changes in EOM myo fi ber cross-sectional
area (Spencer and McNeer 1987 ; Croes et al. 2007 ) . While some MyHC isoform
shifting has been described (Stirn Kranjc et al. 2001 ) , basically there are few changes
in EOM compared to limb skeletal muscle after botulinum toxin injections.
Conversely, the EOM also exhibit robust and rapid regenerative responses after
various perturbations. Acutely after botulinum toxin A injections the EOM exhibit a
rapid and signi fi cant increase in myogenic precursor cells for weeks after injection,
while there is only an abortive regenerative response in similarly treated leg muscle
(Ugalde et al. 2005 ) . The same rapid regenerative response occurs after experimental
EOM surgical recession (Christiansen et al. 2010 ) or resection (Christiansen and
McLoon 2006 ) . A similarly robust response to denervation occurs in other craniofacial
muscles, for example the lateral and posterior cricoarytenoid laryngeal muscles,
after experimental section of the recurrent laryngeal nerve (Shinners et al. 2006 ) .
In some way this process must be important for the maintenance of normal function
in the EOM, as examination of surgically resected muscles from patients with strabismus
have shown signi fi cant alterations in the numbers of activated satellite cells
within these muscles compared to normal control EOM (Antunes-Foschini et al.
2006, 2008 ) . Current studies suggest that there is a population of myogenic precursor
cells in the EOM that may be responsible for this elevated ability to adapt and
remodel (Kallestad et al. 2011 ) . Future work will focus on de fi ning these regenerative
cell populations, and the potential role they play in EOM muscle adaptability
and the relative sparing of the EOM in aging and skeletal muscle pathology.
There are several hypotheses for what controls this on-going process of myo fi ber
remodeling in normal adult EOM. In an in vitro experiment, it was shown that the
EOM precursor cells depend on their speci fi c cranial motor neurons for survival;
they do not survive in the presence of spinal motor neurons (Porter and Hauser
1993 ) . This suggests that speci fi c trophic factors are critical for the maintenance of
mature EOM. Analysis of gene expression differences between EOM and leg muscle
reveals that neurotrophic factors such as insulin-like growth factor (IGF-1) as well
as neurotrophic factor receptors such fi broblast growth factor-receptor I are upregulated
in EOM (Fischer et al. 2002 ) . The up-regulation of IGF-1 receptor compared
to leg skeletal muscle has been demonstrated immunohistochemically
(Anderson et al. 2006 ), and western blot demonstration of the up-regulation of IGF-1
protein in EOM compared to leg skeletal muscle con fi rmed and extended the earlier
gene expression pro fi ling studies (Feng and von Bartheld 2011 ) . Much more work
needs to be done in this area, but from the studies thus far, it appears that, compared
to non-cranial skeletal muscles, the EOM and their corresponding motor neurons
maintain up-regulated levels of neurotrophic molecules.