Myogenic Potential of Extraocular Muscle Satellite Cells

Principal Investigator: Linda McLoon, Ph.D.

Skeletal muscle cells are unique in that individual myofibers contain multiple myonuclei each of which controls the cytoplasm and cell membrane in its immediate vicinity. Each myofiber has associated with it quiescent cells responsible for repair and regeneration, the satellite cells. These cells respond to muscle injury by proliferation and production of myoblasts, which are responsible for regeneration and repair of injured muscles. In contrast to normal adult limb muscle, we have demonstrated that even in aged individuals, a population of activated satellite cells in maintained within normal adult extraocular muscles. These satellite cells apparently fuse into existing myofibers in normal adult extraocular muscle myofibers, resulting in a process of continuous myofiber remodeling throughout adult life. Recent evidence suggests that there are actually two populations of mononucleated cells with myogenic potential within limb skeletal muscle. There is a majority population that is stimulated by injury to proliferate rapidly, the satellite cells, and a minority population, the multipotent precursor cells (mpc), that is slow-cycling and is considered to be more multipotent and stem-cell like. We hypothesize that the in order to maintain this proliferative pool throughout life, extraocular muscles might contain both more satellite cells and more multipotent precursor cells than limb muscle.

 The extraocular muscles express a number of unusual properties compared to limb skeletal muscle. One of the more puzzling aspects of extraocular muscle cell biology is that the extraocular muscles show a distinct propensity for or sparing from various skeletal muscle disorders compared with limb skeletal muscle. In particular, the extraocular muscles are spared in patients with Duchenne's muscular dystrophy and continue to function even after most other skeletal muscles in the body have degenerated. The reason for extraocular muscle sparing in this disorder has not been determined. This sparing coupled with the demonstration that these muscles seem to be able to maintain a proliferating population of satellite cells throughout adult life, supports the idea that the multipotent precursor cells and satellite cells in the extraocular muscles may indeed be different from those of limb skeletal muscles in that they must allow for continued repair in muscular dystrophy patients. We will address this hypothesis by answering the questions. 1. Are there more satellite cells in the EOM compared to limb muscle? 2. Are there more multipotent precursor cells in EOM compared to limb muscle? 3. Do EOM multipotent precursor cells and satellite cells have more myogenic and proliferative potential than those from limb muscle?