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J. L. Walker, L. Zhang, I. Wolff, J. Gerhart, M. George-Weinstein, A. Menko; A Subpopulation of Skeletal Muscle Stem Cells Can Cause Lens Fibrotic Disease. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4768.
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© ARVO (1962-2015); The Authors (2016-present)
The acquisition of a myofibroblast phenotype causes the lens fibrotic disease Posterior Capsule Opacification (PCO). Although the appearance of myofibroblasts is thought to result from an epithelial to mesenchymal transition, the cells which give rise to myofibroblasts and the etiology of PCO disease are unknown. Using an ex vivo lens fibrotic disease model that recapitulates the major features of PCO, including proliferation, migration and expression of mesenchymal markers, we investigated the identity of the cell population responsible for causing lens fibrotic disease. These studies focused on a possible role for skeletal muscle stem cells (skm stem cells), a newly identified population of cells in the lens that express MyoD mRNA and the G8 antigen.
After mock cataract surgery, chick lens capsular bags were pinned to a culture dish as previously described. G8 positive (G8+)/MyoD expressing skm cells were identified by immunolocalization and in situ hybridization. G8+ cells in the ex vivo cultures were ablated by incubation with G8 antibody followed by complement. Expression of the mesenchymal marker -smooth muscle actin (-SMA) was determined by Western blot analysis.
Subpopulations of skm stem cells were identified in niches nestled among the cells of the equatorial zone of the lens. This discovery identified for the first time a cell population in the lens epithelium not derived from the lens epithelial cell. Following mock cataract surgery, the skm cells activated by the wounding emerged from their niches and migrated to the leading edge of the lens epithelial cell monolayer. Ablation of the skm cells blocked the appearance of mesenchymal cells as defined by inhibition of -SMA expression.
Injury associated with mock cataract surgery activates a unique population of skm stem cells, causing them to emerge from their niches to participate in wound healing by migrating to the leading edge of the collectively migrating lens epithelial cell sheet. However, these cells are also responsible for the appearance of -SMA-expressing myofibroblasts in the PCO culture model. These results suggest that the skm stem cells are a cause of lens fibrotic disease.
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