My laboratory focuses on developing pharmacologic treatments for a number of diseases of the eye and orbit. We study craniofacial muscles and their innervation with a focus on extraocular muscles (EOM). Strabismus and Infantile Nystagmus: Eye movement disorders affect the ability of the visual system to process the visual world correctly. Ongoing processes of remodeling in adults suggest that pharmacologic manipulation of the EOM for treatment of strabismus and infantile nystagmus is possible. 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 and other muscle signaling factors results in significantly altered muscle size and force generation that continues for several months after treatment ends. We have treated a strabismic non-human primate and improved its eye alignment, demonstrating proof of principle. However, it is clear that we need to change the brain if these changes are to be sustained. We are now studying how various perturbations in the EOM periphery might alter synapses and perineuronal nets on the ocular motor neurons that innervate these muscles. In a collaborative study, we are assessing how these growth factors alter neuronal firing patterns. We are also comparing whether different growth factors have different effects on the innervating motor neurons. Hopefully, we will be able to generate a new treatment for the millions of children who suffer from these ocular motor disorders.
EOM Sparing in Muscle Diseases: A second project focuses on why the EOM are differentially susceptible or spared in a number of skeletal muscles diseases For example, the EOM are differentially spared in many types of muscular dystrophy. We are examining properties of EOM myogenic precursor cells, and have 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 in vitro and in vivo after various perturbations. It also may be that the myogenic precursor cells in EOM can survive in greater numbers in a more hostile tissue environment, such as in muscle disease, injury, or aging. Results thus far suggest that indeed there is a subpopulation of cells with increased survival capacity.
We are currently working on further identification of this cell population.
Understanding why the EOM are spared in muscular dystrophies has clinical implications for development of future treatments.
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
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;25:873-887.
Graber TG, Kim JH, Grange RW, McLoon LK, Thompson LV. C57BL/6 life span study: age-related declines in muscle power production and contractile velocity. Age (Dordr). 2015 Jun;37(3):9773.
Willoughby CL, Fleuriet J, Walton MM, Mustari MJ, McLoon LK. Adaptability of the Immature Ocular Motor Control System: Unilateral IGF-1 Medial Rectus Treatment. Invest Ophthalmol Vis Sci. 2015 Jun;56(6):3484-96.
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 nonhuman primates. Invest Ophthalmol Vis Sci. 2015 Jun;56(6):3467-83.
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 Apr;3(4).
Walton MM, Mustari MJ, Willoughby CL, McLoon LK. Abnormal activity of neurons in abducens nucleus of strabismic monkeys. Invest Ophthalmol Vis Sci. 2014 Nov 20;56(1):10-9.
McLoon LK, Harandi VM, Brännström T, Andersen PM, Liu JX. Wnt and extraocular muscle sparing in amyotrophic lateral sclerosis. Invest Ophthalmol Vis Sci. 2014 Aug 14;55(9):5482-96.
McDonald AA, Kunz MD, McLoon LK. Dystrophic changes in extraocular muscles after gamma irradiation in mdx:utrophin+/- mice. PLoS One. 2014 Jan 21;9(1):e86424.
Stager DR, McLoon LK, Felius J. Postulating a role for connective tissue elements in inferior oblique overaction. Trans. Am. Ophthalmol. Soc. 2013 Sep;111:119-32.
Hebert SL, Daniel ML, McLoon LK. The role of Pitx2 in maintaining the phenotype of myogenic precursor cells in the extraocular muscles. PMCID: PMC3591328. PLoS One 8(3):e58405, 2013.
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. PMCID: PMC3292383. Invest. Ophthalmol. Vis Sci. 53: 68-75, 2012.
Berg KT, Hunter DG, Bothun ED, Antunes-Foschini R, McLoon LK. Extraocular muscles in subjects with infantile nystagmus: Adaptations at the effector level. Arch. Ophthalmol. 130:1-8, 2012..
McLoon LK, Park H, Kim JH, Pedrosa-Domellöf F, Thompson LV. A continuum of myofibers in adult rabbit extraocular muscle: force, shortening velocity, and patterns of myosin heavy chain co-localization. J. Appl. Physiol. 111: 1178-1189, 2011.
McLoon LK. What experimental embryology can tell us about extraocular muscle development in anophthalmia: At the interface of basic and clinical science. Invited editorial. Arch. Ophthalmol. 129: 1077-1079, 2011.
Anderson BC, Daniel ML, Kendall J, Christiansen SP, McLoon LK. Sustained release of bone morphogenetic protein-4 in adult rabbit extraocular muscle results in decreased force and muscle size: potential for strabismus treatment. Invest. Ophthalmol. Vis. Sci. 52: 4021-4029, 2011.
Kallestad KM, Hebert SL, McDonald AA, Daniel ML, Cu SR, McLoon LK. Sparing of extraocular muscle in aging and dystrophic skeletal muscle: A myogenic precursor cell hypothesis. Exp. Cell Res. 317:873-885, 2011.
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, in press.
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. In press.
McLoon LK, Andrade FH. 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. In press.
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. In press.
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. Mosby Press. pp. 182-207, 2011.
Former Graduate Students:
Christy Willoughby (Ph.D. 2015, Neuroscience, University of Minnesota).
Sandra Alcala (Ph.D. 2009, Neuroscience, University of Minnesota).
Kristen Kallestad (Ph.D. 2009, Neuroscience, University of Minnesota).