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Book: Craniofacial muscles

McLoon, Linda K. / Andrade, Francisco H.

a new framework for understanding the effector side of craniofacial muscle control

2013

Author's details	Linda K. McLoon ; Francisco H. Andrade ed
Language	English
Size	VIII, 345 S. : Ill., graph. Darst.
Publisher	Springer
Publishing place	New York u.a.
Publishing country	United States
Document type	Book
HBZ-ID	HT017420292
ISBN	978-1-4614-4465-7 ; 1-4614-4465-9 ; 9781461444664 ; 1461444667
Database	Catalogue ZB MED Medicine, Health

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Article ; Online: Nystagmus in the B6(CG)Tyr(c-2J)/J Albino Mouse: A Functional and RNA-Seq Analysis.

Johnson, Laura L / Abrahante, Juan E / McLoon, Linda K

Investigative ophthalmology & visual science

2024 Volume 65, Issue 1, Page(s) 26

Abstract: Purpose: Infantile nystagmus syndrome (INS) is a gaze-holding disorder characterized by conjugate, uncontrolled eye oscillations that can result in significant visual acuity loss. INS is often associated with albinism, but the mechanism is unclear. ... ...

Abstract	Purpose: Infantile nystagmus syndrome (INS) is a gaze-holding disorder characterized by conjugate, uncontrolled eye oscillations that can result in significant visual acuity loss. INS is often associated with albinism, but the mechanism is unclear. Albino mice have nystagmus; however, a pigmented mouse with a tyr mutation making it phenotypically albino, the B6(CG)-Tyr(c-2J)/J (B6 albino), had not been tested. We tested optokinetic response (OKR) in B6 albino and control mice. RNA-Seq was performed on extraocular muscles (EOM), tibialis anterior (TA) muscle, abducens (CN6), and oculomotor (CN3) neurons to uncover molecular differences that may contribute to nystagmus. Methods: OKR was measured using an ISCAN system. RNA was isolated from four tissues to identify differentially expressed genes and validated with qPCR and immunohistochemistry. Ingenuity pathway analyses identified top biological pathways. Results: All B6 albino mice tested had nystagmus. Differential RNA expression analysis showed 383 genes differentially expressed in EOM, 70 in CN3, 20 in CN6, and 639 in the TA. Two genes were differentially expressed in all four tissues: wdfy1 and nnt. Differences were validated by qPCR and immunostaining. Conclusions: The tyr mutation in B6 albino mice, genotypically pigmented and phenotypically albino, is sufficient to result in spontaneous nystagmus. The two genes with decreased expression in the B6 albino tissues examined, wdfy1 and nnt, have been implicated in mitochondrial dysfunction and stem cell maintenance in other systems. Their function in extraocular muscle is unknown. These studies suggest that this mouse model of nystagmus may allow molecular identification of candidate nystagmus-related genes.
MeSH term(s)	Animals ; Mice ; RNA-Seq ; Nystagmus, Pathologic/genetics ; Nystagmus, Optokinetic ; Oculomotor Muscles ; RNA/genetics
Chemical Substances	RNA (63231-63-0)
Language	English
Publishing date	2024-01-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.65.1.26
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Article ; Online: Nystagmus Associated With the Absence of MYOD Expression Across the Lifespan in Extraocular and Limb Muscles.

Johnson, Laura L / Hebert, Sadie / Kueppers, Rachel B / McLoon, Linda K

Investigative ophthalmology & visual science

2023 Volume 64, Issue 12, Page(s) 24

Abstract: Purpose: The extraocular muscles (EOMs) undergo significant levels of continuous myonuclear turnover and myofiber remodeling throughout life, in contrast to limb skeletal muscles. Activation of the myogenic pathway in muscle precursor cells is ... ...

Abstract	Purpose: The extraocular muscles (EOMs) undergo significant levels of continuous myonuclear turnover and myofiber remodeling throughout life, in contrast to limb skeletal muscles. Activation of the myogenic pathway in muscle precursor cells is controlled by myogenic transcription factors, such as MYOD. Limb muscles from MyoD-/- mice develop normally but have a regeneration defect, and these mice develop nystagmus. We examined MyoD-/- mice to determine if they have an aging phenotype. Methods: Eye movements of aging MyoD-/- mice and littermate controls (wild type) were examined using optokinetic nystagmus (OKN). We assessed limb muscle function, changes to myofiber number, mean cross-sectional area, and abundance of the PAX7 and PITX2 populations of myogenic precursor cells. Results: Aging did not significantly affect limb muscle function despite decreased mean cross-sectional areas at 18+ months. Aging wild type mice had normal OKN responses; all aging MyoD-/- mice had nystagmus. With OKN stimulus present, the MyoD-/- mice at all ages had shorter slow phase durations compared to wild type age matched controls. In the dark, the MyoD-/- mice had a shorter slow phase duration with age. This correlated with significantly decreased fiber numbers and cross-sectional areas. The EOM in MyoD-/- mice had increased numbers of PAX7-positive satellite cells and significantly decreased PITX2-positive myonuclei. Conclusions: The absence of MYOD expression in aging mice causes a decrease in on-going myofiber remodeling, EOM fiber size, and number, and is associated with the development of spontaneous nystagmus. These results suggest that muscle-specific mutations can result in nystagmus, with increasing aging-related changes in the MyoD-/- EOM.
MeSH term(s)	Animals ; Mice ; Longevity ; Nystagmus, Pathologic ; Aging ; Nystagmus, Optokinetic ; Muscle, Skeletal
Language	English
Publishing date	2023-09-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.64.12.24
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Article ; Online: Effect of Fibroblast Growth Factor 2 on Extraocular Muscle Structure and Function.

Rudell, Jolene C / McLoon, Linda K

Investigative ophthalmology & visual science

2021 Volume 62, Issue 9, Page(s) 34

Abstract: Purpose: Mutations in the fibroblast growth factor (FGF) receptor can result in strabismus, but little is known about how FGFs affect extraocular muscle structure and function. These were assessed after short-term and long-term exposure to exogenously ... ...

Abstract	Purpose: Mutations in the fibroblast growth factor (FGF) receptor can result in strabismus, but little is known about how FGFs affect extraocular muscle structure and function. These were assessed after short-term and long-term exposure to exogenously applied FGF2 to determine the effect of enhanced signaling. Methods: One superior rectus muscle of adult rabbits received either a series of three injections of 500 ng, 1 µg, or 5 µg FGF2 and examined after 1 week, or received sustained treatment with FGF2 and examined after 1, 2, or 3 months. Muscles were assessed for alterations in force generation, myofiber size, and satellite cell number after each treatment. Results: One week after the 5 µg FGF2 injections, treated muscles showed significantly increased force generation compared with naïve controls, which correlated with increased myofiber cross-sectional areas and Pax7-positive satellite cells. In contrast, 3 months of sustained FGF2 treatment resulted in decreased force generation, which correlated with decreased myofiber size and decreased satellite cells compared with naïve control and the untreated contralateral side. Conclusions: FGF2 had distinctly different effects when short-term and long-term treatments were compared. The decreased size and ability to generate force correlated with decreased myofiber areas seen in individuals with Apert syndrome, where there is sustained activation of FGF signaling. Knowing more about signaling pathways critical for extraocular muscle function, development, and disease will pave the way for improved treatment options for strabismus patients with FGF abnormalities in craniofacial disease, which also may be applicable to other strabismus patients.
MeSH term(s)	Animals ; Fibroblast Growth Factor 2/administration & dosage ; Injections, Intramuscular ; Models, Animal ; Muscle Contraction/drug effects ; Muscle Contraction/physiology ; Muscle Fibers, Skeletal/metabolism ; Muscle Fibers, Skeletal/physiology ; Oculomotor Muscles/cytology ; Oculomotor Muscles/physiology ; Rabbits
Chemical Substances	Fibroblast Growth Factor 2 (103107-01-3)
Language	English
Publishing date	2021-10-21
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.62.9.34
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Article ; Online: Effects of D-serine treatment on outer retinal function.

Torres Jimenez, Nathalia / Miller, Robert F / McLoon, Linda K

Experimental eye research

2021 Volume 211, Page(s) 108732

Abstract: The role of the N-Methyl-D-Aspartate Receptor (NMDAR) in the outer retina is unclear despite expression of the NMDAR-complex and its subunits in the outer retina. The flash-electroretinogram (fERG) offers a non-invasive measurement of the retinal field ... ...

Abstract	The role of the N-Methyl-D-Aspartate Receptor (NMDAR) in the outer retina is unclear despite expression of the NMDAR-complex and its subunits in the outer retina. The flash-electroretinogram (fERG) offers a non-invasive measurement of the retinal field potentials of the outer retina that can serve to clarify NMDAR contribution to early retinal processing. The role of the NMDAR in retinal function was assessed using a genetic mouse model for NMDAR hypofunction (SR
MeSH term(s)	Animals ; Electroretinography/drug effects ; Female ; Male ; Mesopic Vision/physiology ; Mice ; Mice, Knockout ; Photic Stimulation ; Racemases and Epimerases ; Receptors, N-Methyl-D-Aspartate/metabolism ; Retina/physiology ; Serine/pharmacology
Chemical Substances	Receptors, N-Methyl-D-Aspartate ; Serine (452VLY9402) ; Racemases and Epimerases (EC 5.1.-) ; serine racemase (EC 5.1.1.16)
Language	English
Publishing date	2021-08-20
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80122-7
ISSN	1096-0007 ; 0014-4835
ISSN (online)	1096-0007
ISSN	0014-4835
DOI	10.1016/j.exer.2021.108732
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Article ; Online: Visualizing Neuronal Adaptation Over Time After Treatment of Strabismus.

Fleuriet, Jérome / McLoon, Linda K

Investigative ophthalmology & visual science

2018 Volume 59, Issue 12, Page(s) 5022–5024

MeSH term(s)	Adaptation, Physiological ; Animals ; Haplorhini ; Neuronal Plasticity ; Strabismus ; Vision, Binocular
Language	English
Publishing date	2018-10-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.18-25651
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Article ; Online: Morphological Differences in the Inferior Oblique Muscles from Subjects with Over-elevation in Adduction.

Rudell, Jolene C / Stager, David / Felius, Joost / McLoon, Linda K

Investigative ophthalmology & visual science

2020 Volume 61, Issue 6, Page(s) 33

Abstract: Purpose: We examined inferior oblique muscles from subjects with over-elevation in adduction for characteristics that might shed light on the potential mechanisms for their abnormal eye position.: Methods: The inferior oblique muscles were obtained ... ...

Abstract	Purpose: We examined inferior oblique muscles from subjects with over-elevation in adduction for characteristics that might shed light on the potential mechanisms for their abnormal eye position. Methods: The inferior oblique muscles were obtained at the time of surgery in subjects diagnosed with either primary inferior oblique overaction or Apert syndrome. The muscles were frozen and processed for morphometric analysis of myofiber size, central nucleation, myosin heavy chain (MyHC) isoform expression, nerve density, and numbers of neuromuscular junctions per muscle section. Results: The inferior oblique muscles from subjects with Apert Syndrome were smaller, and had a much more heterogeneous profile relative to myofiber cross-sectional area compared to controls. Increased central nucleation in the Apert syndrome muscles suggested on-going myofiber regeneration or reinnervation over time. Complex changes were seen in the MyHC isoform patterns that would predict slower and more sustained contractions than in the control muscles. Nerve fiber densities were significantly increased compared to controls for the muscles with primary inferior oblique overaction and Apert syndrome that had no prior surgery. The muscles from Apert syndrome subjects as well as those with primary inferior oblique overaction with no prior surgery had significantly elevated numbers of neuromuscular junctions relative to the whole muscle area. Conclusions: The muscles from both sets of subjects were significantly different from control muscles in a number of properties examined. These data support the view that despite similar manifestations of eye misalignment, the potential mechanism behind the strabismus in these subjects is significantly different.
MeSH term(s)	Adult ; Child ; Child, Preschool ; Eye Movements/physiology ; Female ; Humans ; Male ; Oculomotor Muscles/diagnostic imaging ; Oculomotor Muscles/physiopathology ; Oculomotor Muscles/surgery ; Ophthalmologic Surgical Procedures/methods ; Strabismus/diagnosis ; Strabismus/physiopathology ; Strabismus/surgery ; Treatment Outcome ; Vision, Binocular/physiology
Language	English
Publishing date	2020-06-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.61.6.33
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Article ; Online: Childhood Onset Strabismus: A Neurotrophic Factor Hypothesis.

Rudell, Jolene C / Fleuriet, Jérome / Mustari, Michael J / McLoon, Linda K

Journal of binocular vision and ocular motility

2021 Volume 71, Issue 2, Page(s) 35–40

Abstract: Strabismus is a genetically heterogeneous disorder with complex molecular and neurophysiological causes. Evidence in the literature suggests a strong role for motor innervation in the etiology of strabismus, which connects central neural processes to the ...

Abstract	Strabismus is a genetically heterogeneous disorder with complex molecular and neurophysiological causes. Evidence in the literature suggests a strong role for motor innervation in the etiology of strabismus, which connects central neural processes to the peripheral extraocular muscles. Current treatments of strabismus through surgery show that an inherent sensorimotor plasticity in the ocular motor system decreases the effectiveness of treatment, often driving eye alignment back toward its misaligned pre-surgical state by altering extraocular muscle tonus. There is recent interest in capitalizing on existing biological processes in extraocular muscles to overcome these compensatory mechanisms. Neurotrophins are trophic factors that regulate survival and development in neurons and muscle, including extraocular muscles. Local administration of neurotrophins to extraocular muscles partially reversed strabismus in an animal model of strabismus. The hypothesis is that sustained release of neurotrophins gives more time for the ocular motor system to adapt to a slow change in alignment in the desired direction. The effect of neurotrophins on extraocular muscles is complex, as different neurotrophic factors have diverse effects on extraocular muscle contraction profiles, patterns of innervation, and density of extraocular muscle precursor cells. Neurotrophic factors show promise as a therapeutic option for strabismus, which may help to improve treatment outcomes and offset devastating amblyopia and psychosocial effects of disease in strabismus patients.
MeSH term(s)	Adaptation, Physiological ; Amblyopia ; Animals ; Child ; Humans ; Nerve Growth Factors ; Oculomotor Muscles/surgery ; Strabismus/surgery
Chemical Substances	Nerve Growth Factors
Language	English
Publishing date	2021-04-19
Publishing country	United States
Document type	Journal Article
ISSN	2576-1218
ISSN (online)	2576-1218
DOI	10.1080/2576117X.2021.1893585
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Article ; Online: Development of Nystagmus With the Absence of MYOD Expression in the Extraocular Muscles.

Johnson, Laura L / Kueppers, Rachel B / Shen, Erin Y / Rudell, Jolene C / McLoon, Linda K

Investigative ophthalmology & visual science

2021 Volume 62, Issue 13, Page(s) 3

Abstract: Purpose: Myoblast determination protein 1 (MYOD) is a critical myogenic regulatory factor in muscle development, differentiation, myofiber repair, and regeneration. As the extraocular muscles significantly remodel their myofibers throughout life ... ...

Abstract	Purpose: Myoblast determination protein 1 (MYOD) is a critical myogenic regulatory factor in muscle development, differentiation, myofiber repair, and regeneration. As the extraocular muscles significantly remodel their myofibers throughout life compared with limb skeletal muscles, we hypothesized that the absence of MYOD would result in their abnormal structure and function. To assess structural and functional changes in the extraocular muscles in MyoD-/- mice, fiber size and number and optokinetic nystagmus reflex (OKN) responses were examined. Methods: OKN was measured in MyoD-/- mice and littermate wild-type controls at 3, 6, and 12 months. The extraocular muscles were examined histologically for changes in mean myofiber cross-sectional area, total myofiber number, and nuclei immunostained for PAX7 and PITX2, markers of myogenic precursor cells. Results: The MyoD-/- mice developed nystagmus, with both jerk and pendular waveforms, in the absence and in the presence of moving visual stimulation. At 12 months, there were significant losses in mean myofiber cross-sectional area and in total number of orbital layer fibers in all rectus muscles, as well as in global layer fibers in the superior and inferior rectus muscles. Haploinsufficient mice showed abnormal OKN responses. PITX2-positive cell entry into myofibers of the MyoD-/- mice was significantly reduced. Conclusions: This study is the first demonstration of the development of nystagmus in the constitutive absence of expression of the muscle-specific transcription factor MYOD. We hypothesize that myofiber loss over time may alter anterograde and/or retrograde communication between the motor nerves and extraocular muscles that are critical for maintaining normalcy of extraocular muscle function.
MeSH term(s)	Animals ; Disease Models, Animal ; Follow-Up Studies ; Gene Expression Regulation ; Mice ; MyoD Protein/biosynthesis ; MyoD Protein/genetics ; Nystagmus, Pathologic/diagnosis ; Nystagmus, Pathologic/genetics ; Nystagmus, Pathologic/metabolism ; Oculomotor Muscles/diagnostic imaging ; Oculomotor Muscles/metabolism
Chemical Substances	MyoD Protein ; MyoD1 myogenic differentiation protein
Language	English
Publishing date	2021-10-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.62.13.3
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Article: Demystifying Graduate School: Navigating a PhD in Neuroscience and Beyond.

McLoon, Linda K / Redish, A David

Journal of undergraduate neuroscience education : JUNE : a publication of FUN, Faculty for Undergraduate Neuroscience

2018 Volume 16, Issue 3, Page(s) A203–A209

Abstract: The decision to apply to a PhD-granting graduate program is both exciting and daunting. Understanding what graduate programs look for in an applicant will increase the chance of successful admission into a PhD program. It is also helpful for an applicant ...

Abstract	The decision to apply to a PhD-granting graduate program is both exciting and daunting. Understanding what graduate programs look for in an applicant will increase the chance of successful admission into a PhD program. It is also helpful for an applicant to understand what graduate training will look like once they matriculate into a PhD program to ensure they select programs that will help them reach their career objectives. This article focuses specifically on PhD programs in neuroscience, and while we use our program, the Graduate Program in Neuroscience at the University of Minnesota, as an example, most of what we describe is applicable to biomedical graduate programs generally. In order to ensure that our description of graduate programs is typical of neuroscience graduate programs generally, we surveyed the online websites of 52 neuroscience graduate programs around the U. S. and include our observations here. We will examine what graduate schools look for in an applicant, what to expect once admitted into a PhD graduate program, and the potential outcomes for those who successfully complete their PhD in neuroscience.
Language	English
Publishing date	2018-09-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2577251-X
ISSN	1544-2896
ISSN	1544-2896
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