Linda K. McLoon, PhD

Professor, Department of Ophthalmology and Visual Neurosciences

Linda K. McLoon

Contact Info

mcloo001@umn.edu

Office Phone 612-626-0777

Fax 612-626-0781

Office Address:
Department of Ophthalmology & Visual Neurosciences
374 Lions Research Building
2001 6th Street S.E.
Minneapolis, Minnesota 55455

Graduate School, University of Illinois at the Medical Center

Research

Research Summary/Interests

Craniofacial muscles

I have been studying craniofacial muscles and their innervation for over 30 years, and specifically focusing on extraocular muscles (EOM) since 1996.

My acknowledged expertise in EOM is demonstrated by my serving as section editor for the Orbit sections (20 chapters) of the large Elsevier Encyclopedia of the Eye, providing the EOM chapter in the new edition of Adler’s Physiology of the Eye, and co-editing a book to be published by Springer on craniofacial muscles. The EOM are differentially spared in multiple types of muscular dystrophy. My lab also has been examining properties of EOM myogenic precursor cells, and has isolated a candidate population which may be responsible for this sparing. We are looking at the rates of turnover of these cells, as well as their specific cell biological properties. We were the first laboratory to develop this hypothesis. My laboratory made the novel observation that contrary to limb skeletal muscle, adult EOM continue to remodel throughout life by adding new myonuclei to existing myofibers. Based on these studies, it seemed reasonable that these ongoing processes of remodeling in adults would allow pharmacologic manipulation of the EOM for treatment of strabismus. No new pharmacologic treatment for strabismus has been developed since botulinum toxin in the 1970s, and there is currently no pharmacological approach to strengthen an underacting EOM. We were the first lab to demonstrate that direct muscular injection of insulin growth factors I or II results in significant increase muscle force generation and myofiber size. Sustained delivery of these agents results in significant increases in muscle size and force generation that continues for several months after treatment ends. Strabismus involves both muscles that are overacting as well as underacting. For the treatment of overacting muscles, temporary weakening is needed. We recently showed that specific myogenic signaling factors, e.g. bone morphogenetic factor-4 (BMP4), weaken EOM after acute and chronic delivery. This would allow treatment of agonist-antagonist muscle pairs with factors that could weaken the overacting muscle and strengthen the underacting muscle. We recently demonstrated that EOM removed from patients with strabismus or infantile nystagmus has properties different from normal human EOM. We continue to examine human muscle specimens from these patients to determine if these abnormal properties can be modulated by pharmacologic treatments. In summary, we have produced a large body of work demonstrating the feasibility of growth factor delivery for pharmacologic treatment of strabismus. There is a great deal of interest in the clinical applications of this work.

Research interests:

  • Development of pharmacologic treatments for strabismus and infantile nystagmus syndrome
  • Extraocular muscles and their stem cells
  • Sparing of the extraocular muscles in muscular dystrophies
  • Molecular control of extraocular muscle properties and how these are affected in strabismus and nystagmus

Publications

Publications

For a list of publications, see PubMed.

Peer-Reviewed Publications

  • McDonald AA, Hebert SL, McLoon LK. Sparing of the extraocular muscles in mdx mice with absent or reduced utrophin expression: A life span analysis. PMID: 26429098. Neuromusc. Disord. 2015; Sep 6. Pii: S0960-8966(15)00713.0. doi: 10.1016/j.nmd.2015.09.001.
  • Willoughby CL, Fleuriet J, Walton MM, Mustari MJ, McLoon LK. Adaptability of the immature ocular motor control system: Unilateral IGF-I medial rectus treatment. Invest. Ophthalmol. Vis. Sci. 2015;56: In press.
  • Willoughby CL, Fleuriet J, Walton MM, Mustari MJ, McLoon LK. Adaptation of slow myofibers: The effect of sustained BDNF treatment of extraocular muscles in infant non-human primates. Invest. Ophthalmol. Vis. Sci. 2015;56: In press.
  • McDonald AA, Hebert SL, Kunz MD, Ralles SJ, McLoon LK. Disease course in mdx:utrophin+/- mice: Comparison of three mouse models of Duchenne muscular dystrophy. Physiol. Rep. 2015;3(4):e12391.
  • Graber TG, Kim JH, Grange RW, McLoon LK, Thompson LV. C57BL/6 lifespan study: Age-related changes in muscle power production and contractile velocity. PMID: 25893911. Age. 2015;37:9773. doi 10.1007/s11357-015-9773-1.
  • Walton MMG, Mustari J, Willoughby CL, McLoon LK. Abnormal activity of neurons in the abducens nucleus of strabismic monkeys. PMC4283474.. Invest. Ophthalmol. Vis. Sci. 2015;56:10-19. Highlighted article: Cullen K; IOVS 2015;56:20.
  • McDonald AA, Kunz MD, McLoon LK. Dystrophic changes in extraocular muscles after gamma irradiation in mdx:utrophin+/- mice. PMC3897728. PLoS One. 2014;9(1):e86424.
  • McLoon LK, Harandi V, Brännström T, Andersen PM, Liu JX. Wnt and extraocular muscle sparing in amyotrophic lateral sclerosis. PMID: 25125606. Invest. Ophthalmol. Vis. Sci. 2014;55:5482-5496.
  • Hebert SL, Daniel ML, McLoon LK. The role of Pitx2 in maintaining the phenotype of myogenic precursor cells in the extraocular muscles. PMC3591328. PLoS One. 2013;8(3):e58405.
  • Stager DR, McLoon LK, Felius J. Postulating a role for connective tissue elements in inferior oblique overaction. PMC3812716. Trans. Am. Ophthalmol. Soc. 2013;111:70-81.
  • Willoughby CL, Christiansen SP, Mustari MJ, McLoon LK. Effects of the sustained release of IGF-1 on extraocular muscle of the infant non-human primate: Adaptations at the effector organ level. PMC3292383. Invest. Ophthalmol. Vis Sci. 2012;53:68-75. 

Books

  • Craniofacial Muscles: A New Framework for Understanding the Effector Side of Craniofacial Muscle Control. Eds: LK McLoon, F Andrade. Springer, 2012. 338 pages. Edited entire book, Wrote 4 chapters.

Chapters in Books

  • Andrade FH, McLoon LK. The Craniofacial Muscles: Arguments for Uniqueness. In: Craniofacial Muscles: A New Framework for Understanding the Effector Side of Craniofacial Muscles. Eds: LK McLoon, F Andrade. Springer, 2012; pp. 3-7.
  • McLoon LK, Willoughby CL, Andrade FH. Extraocular Muscles: Structure and Function. In: Craniofacial Muscles: A New Framework for Understanding the Effector Side of Craniofacial Muscles. Eds: LK McLoon, F Andrade. Springer, 2012; pp. 31-88.
  • Hebert SL, Willoughby CL, Andrade FH, McLoon LK. Masticatory Muscles: Response to Neuromuscular Diseases and Specific Pathologies. In: Craniofacial Muscles: A New Framework for Understanding the Effector Side of Craniofacial Muscles. Eds: LK McLoon, F Andrade. Springer, 2012; pp. 131-138.
  • McLoon LK, Andrade FH. Comparison of craniofacial Muscles: A Unifying Hypothesis. In: Craniofacial Muscles: A New Framework for Understanding the Effector Side of Craniofacial Muscles. Eds: LK McLoon, F Andrade. Springer, 2012; pp. 325-335.
  • McLoon LK. The Extraocular Muscles, Chapter 7, In: Adler’s Physiology of the Eye, 11th edition, Eds: Kaufman P, Alm A, Levin LA, Nilsson S, Ver Hoeve J, Wu SM. Elsevier. New York. pp. 182-207, 2011.
  • McLoon LK and Christiansen SP. Extraocular Muscles: Extraocular Muscle Anatomy. In: Ocular Periphery and Disorders, (ed. DA Dartt, P Bix, P D’Amore, R Dana, LK McLoon, JY Niederkorn) Oxford: Academic Press. pp. 17-26, 2011.
  • Christiansen SP, McLoon LK. Extraocular Muscles: Functional Assessment in the Clinic, Elsevier Encyclopedia of the Eye In: Ocular Periphery and Disorders, (ed. DA Dartt, P Bix, P D’Amore, R Dana, LK McLoon, JY Niederkorn) Oxford: Academic Press. 2011; pp. 45-48. 
  • Semmer AE, McLoon LK, Lee MS. Orbital Vascular Anatomy. In: Immunology, Inflammation, and Diseases of the Eye, (ed. DA Dartt, R Dana, P D’Amore, J Niederkorn) Oxford: Academic Press; 2011.
  • Anderson BC, McLoon LK. The Orbit: Cranial Motor Nerves and Autonomic Innervation. In: Encyclopedia of the Eye, (ed. DA Dartt) Oxford: Academic Press; Vol 1:537-548, 2010.
  • McLoon LK and Christiansen SP. The Orbit: Extraocular Muscle Anatomy. In: Encyclopedia of the Eye, (ed. DA Dartt) Oxford: Academic Press; Vol 2:89-98, 2010. 

Presentations

National Invited Oral Presentations (Invited Seminars and National Professional Meetings)

  • “Examination of Extraocular Muscles and Their Innervation from Subjects with Infantile Nystagmus Syndrome and Optic Nerve Hypoplasia” Platform Presentation, Association for Research in Vision and Ophthalmology Annual Meeting, Denver, CO. May 2015
  • “Cellular Changes in Extraocular Muscle in Strabismus and Nystagmus”, Mini-symposium Invited Speaker, Association for Research in Vision and Ophthalmology Annual meeting, Denver, CO. May 2015
  • “Extraocular Muscles as Windows into Ocular Motor Function” Invited Seminar Speaker, University of Houston College of Optometry, Houston, Texas February 2015
  • “Up-regulation of a Unique Population of Myogenic Precursor Cells in Pax7-Depleted Extraocular Muscles.” FASEB Conference on Skeletal Muscle Satellite and Stem Cells, Colorado Springs, CO. July 2014
  • “Examination of Extraocular Muscles and Their Innervation from Subjects with Infantile Nystagmus Syndrome and Albinism”, Platform Presentation, Association for Research in Vision and Ophthalmology Annual Meeting, Orlando, Florida May 2014
  • “Diversity of Myogenic Precursor Cells in Extraocular Muscle: Potential Functional Implications”, Muscle Forum, University of Kentucky, Lexington, Kentucky. January 2014
  • “A morphometric analysis of the inferior oblique muscle in patients with inferior oblique overaction”, Platform Presentation, Association for Research in Vision and Ophthalmology Annual Meeting, Seattle, Washington. May 2013.
  • “Dynamic Cell Biology of the Extraocular Muscles”, Vision Training Grant Invited Speaker, Department of Biological Structure, University of Washington, Seattle, Washington. March 2013
  • “Changing the Paradigm for Understanding Extraocular Muscles and Strabismus”, Grand Rounds, Department of Ophthalmology, University of Michigan, Ann Arbor, Michigan. March 2013
  • “Dynamic Cell Biology of the Extraocular Muscles”, Department of Ophthalmology, University of Michigan, Ann Arbor, Michigan. March 2013

Teaching

Courses

NSC 5203: Neuroscience of Vision (Fall semester)