Linda McLoon, PhD

Professor, Department of Ophthalmology and Visual Neurosciences

Linda McLoon

Contact Info

mcloo001@umn.edu

Office Phone 612-626-0777

Fax 612-626-0781

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

Graduate School, University of Illinois at the Medical Center

Summary

Awards & Recognition

  • Scientific Review Committee, Fight for Sight, 2011-present
  • Honorary Member (one of 6 so honored), American Association for Pediatric Ophthalmology and Strabismus, 2012-present
  • Elected to Board of Trustees, Association for Research in Vision and Ophthalmology, 2011-present
  • Gold Fellow, Association for Research in Vision and Ophthalmology, 2009-present
  • Lew Wasserman Mid-Career Merit Award, Research to Prevent Blindness, 2005-06
  • American Society of Ophthalmic Plastic and Reconstructive Surgery Research Award for the most outstanding research published in the journal in 2002.

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

Verma, M, Asakura, Y, Murakonda, BSR, Pengo, T, Latroche, C, Chazaud, B, McLoon, LK & Asakura, A 2018, 'Muscle Satellite Cell Cross-Talk with a Vascular Niche Maintains Quiescence via VEGF and Notch Signaling' Cell Stem Cell, vol. 23, no. 4, pp. 530-543.e9. https://doi.org/10.1016/j.stem.2018.09.007

Fleuriet, J & McLoon, LK 2018, 'Visualizing neuronal adaptation over time after treatment of strabismus' Investigative Ophthalmology and Visual Science, vol. 59, no. 12, pp. 5022-5024. https://doi.org/10.1167/iovs.18-25651

Fitzpatrick, KR, Cucak, A & McLoon, LK 2018, 'Changing muscle function with sustained glial derived neurotrophic factor treatment of rabbit extraocular muscle' PLoS One, vol. 13, no. 8, e0202861. https://doi.org/10.1371/journal.pone.0202861

McLoon, LK, Vicente, A, Fitzpatrick, KR, Lindström, M & Pedrosa Domellöf, F 2018, 'Composition, architecture, and functional implications of the connective tissue network of the extraocular muscles' Investigative Ophthalmology and Visual Science, vol. 59, no. 1, pp. 322-329. https://doi.org/10.1167/iovs.17-23003

Olson, RM, Mokhtarzadeh, A, McLoon, LK & Harrison, AR 2019, 'Effects of Repeated Eyelid Injections with Botulinum Toxin A on Innervation of Treated Muscles in Patients with Blepharospasm' Current Eye Research, vol. 44, no. 3, pp. 257-263. https://doi.org/10.1080/02713683.2018.1543707

Hebert, SL, Fitzpatrick, KR, McConnell, SA, Cucak, A, Yuan, C & McLoon, LK 2017, 'Effects of retinoic acid signaling on extraocular muscle myogenic precursor cells in vitro' Experimental Cell Research, vol. 361, no. 1, pp. 101-111. https://doi.org/10.1016/j.yexcr.2017.10.007

McLoon, LK, Christiansen, SP, Ghose, GM, Das, VE & Mustari, MJ 2016, 'Improvement of Eye Alignment in Adult Strabismic Monkeys by Sustained IGF-1 Treatment' Investigative ophthalmology & visual science, vol. 57, no. 14, pp. 6070-6078. https://doi.org/10.1167/iovs.16-19739

Nelson, KR, Stevens, SM & McLoon, LK 2016, 'Prolongation of relaxation time in extraocular muscles with brain derived neurotrophic factor in adult rabbit' Investigative Ophthalmology and Visual Science, vol. 57, no. 13, pp. 5834-5842. https://doi.org/10.1167/iovs.16-19679

Yuan, C, Bothun, ED, Hardten, DR, Tolar, J & McLoon, LK 2016, 'A novel explanation of corneal clouding in a bone marrow transplant-treated patient with Hurler syndrome' Experimental Eye Research, vol. 148, pp. 83-89. https://doi.org/10.1016/j.exer.2016.05.022

McLoon, LK, Willoughby, CL, Anderson, JS, Bothun, ED, Stager, D, Felius, J, Lee, H & Gottlob, I 2016, 'Abnormally small neuromuscular junctions in the extraocular muscles from subjects with idiopathic nystagmus and nystagmus associated with albinism' Investigative Ophthalmology and Visual Science, vol. 57, no. 4, pp. 1912-1920. https://doi.org/10.1167/iovs.16-19129

Teaching

Courses

NSC 5203: Neuroscience of Vision (Fall semester)