Linda McLoon, Ph.D.

Professor, Departments of Ophthalmology and Neuroscience

E-mail: mcloo001@umn.edu

Website: www.lkmcloon.umn.edu


Research Interests:

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.


Selected Publications:

(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)

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. PMID: 22125277. Invest. Ophthalmol. Vis Sci. 53: 68-75, 2012.

Berg KT, Hunter DG, Bothun ED, Rosalia Antunes-Foschini, McLoon LK. Extraocular muscles in subjects with infantile nystagmus: Adaptations at the effector level. PMID: 22411664. Arch. Ophthalmol. 130:1-8, 2012.

Willoughby CL, Ralles S, Christiansen SP, McLoon LK. Effects of sequential injections of hepatocyte growth factor and insulin-like growth factor-I on adult rabbit extraocular muscle. J AAPOS 16:354-360, 2012.

McLoon LK, Park HN, Kim JH, Pedrosa-Domellof 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. 2011 Jul 21.

Anderson BC, Daniel ML, Kendall JD, 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. 2011 Jun 8;52(7):4021-9. Print 2011 Jun.

Kallestad KM, Hebert SL, McDonald AA, Daniel ML, Cu SR, McLoon LK. Sparing of extraocular muscle in aging and muscular dystrophies: a myogenic precursor cell hypothesis. Exp Cell Res. 2011 Apr 1;317(6):873-85. Epub 2011 Jan 27.

Harrison AR, Berbos Z, Zaldivar RA, Anderson BC, Semmer M, Lee MS, McLoon LK. Modulating neuromuscular junction density changes in botulinum toxin-treated orbicularis oculi muscle. Invest Ophthalmol Vis Sci. 2011 Feb 23;52(2):982-6. Print 2011 Feb.

Alcala-Barraza SR, Lee MS, Hanson LR, McDonald AA, Frey WH, McLoon LK. Intranasal delivery of neurotrophic factors BDNF, CNTF, EPO and NT-4 to the CNS. PMID: 19807216. J Drug Targeting 18:179-190, 2010.
 
Harrison AR, Lee MS, McLoon LK. Effects of elevated thyroid hormone levels on rabbit extraocular muscles. PMID: 19628737. Invest. Ophthalmol. Vis. Sci. 51: 183-191, 2010.
 
Kallestad KM, McLoon LK. Defining the heterogeneity of skeletal muscle-derived side and main population cells isolated immediately ex vivo. PMID: 20020527. J. Cell. Physiol. 222:676-684, 2010.

Christiansen SP, Antunes-Foschini RS, McLoon LK. Effect of recession versus tenotomy surgery without recession in adult rabbit extraocular muscle.  PMID: 20538996. Invest. Ophthalmol. Vis. Sci. 51: 5646-5656, 2010.

Book Chapters:

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.


Current Graduate Students:

Christy Willoughby (Neuroscience, University of Minnesota).

Former Graduate Students:

Sandra Alcala (Ph.D. 2009, Neuroscience, University of Minnesota).

Kristen Kallestad (Ph.D. 2009, Neuroscience, University of Minnesota).