Effects of Glial Cell Line-Derived Neurotrophic Factor and Ciliary Neurotrophic Factor on Extraocular and Limb Muscle Precursor Cells

Abstract

Summary

Myogenic precursor cells within skeletal muscles are responsible for the maintenance of skeletal muscle over a lifetime. Neurotrophic and growth factors play critical roles in this maintenance and in responses of myogenic precursor cells. Both glial cell line-derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) play roles in the maintenance and/or development of strabismus, yet few studies have examined their roles in the control of myogenic precursor cell proliferation and differentiation. Two populations of myogenic precursor cells were isolated from extraocular and leg muscle by fluorescence-activated cell sorting: EECD34 cells, largely PITX2-positive, and PAX7-positive cells. Cultures were treated with GDNF or CNTF and processed immunohistochemically to determine proliferation and differentiation rates. Neither GDNF nor CNTF affected cell proliferation rates for either muscle. Both treatments impacted cell differentiation by increasing multinucleated cell number, with TA-derived precursor cells producing cells containing large numbers of nuclei and EOM-derived precursor cells producing shorter multinucleated fibers with fewer nuclei. These differences may explain the presence of extremely short myofibers within normal adult EOM compared with limb muscle. As GDNF and CNTF are downregulated in strabismic muscles, data suggest that myofiber length homeostasis may be disrupted in strabismic EOM and suggest possible approaches for strabismus treatment: