Abstract
Posterior capsule opacification (PCO) is a vision impairing condition that arises in some patients following cataract surgery. The fibrotic form of PCO is caused by myofibroblasts that may emerge in the lens years after surgery. In the chick embryo lens, myofibroblasts are derived from Myo/Nog cells that are identified by their expression of the skeletal muscle specific transcription factor MyoD, the bone morphogenetic protein inhibitor Noggin, and the epitope recognized by the G8 monoclonal antibody. The goal of this study was to test the hypothesis that depletion of Myo/Nog cells will prevent the accumulation of myofibroblasts in human lens tissue. Myo/Nog cells were present in anterior, equatorial and bow regions of the human lens, cornea and ciliary processes. In anterior lens tissue removed by capsulorhexis, Myo/Nog cells had synthesized myofibroblast and skeletal muscle proteins, including vimentin, MyoD and sarcomeric myosin. Alpha smooth muscle actin (α-SMA) was detected in a subpopulation of Myo/Nog cells. Areas of the capsule denuded of epithelial cells were surrounded by Myo/Nog cells. Some of these cell free areas contained a wrinkle in the capsule. Depletion of Myo/Nog cells eliminated cells expressing skeletal muscle proteins in 5-day cultures but did not affect cells immunoreactive for beaded filament proteins that accumulate in differentiating lens epithelial cells. Transforming growth factor-betas 1 and 2 that mediate an epithelial-mesenchymal transition, did not induce the expression of skeletal muscle proteins in lens cells following Myo/Nog cell depletion. This study demonstrates that Myo/Nog cells in anterior lens tissue removed from cataract patients have undergone a partial differentiation to skeletal muscle. Myo/Nog cells appear to be the source of skeletal muscle-like cells in explants of human lens tissue. Targeting Myo/Nog cells with the G8 antibody during cataract surgery may reduce the incidence of PCO.
Highlights
Posterior capsule opacification (PCO) is a vision impairing condition that arises in some patients following cataract surgery [1,2]
Several families of molecules have been implicated in the emergence of myofibroblasts in lens tissue [43], including transforming growth factor beta (TGF-b) that induces an epithelial to mesenchymal transition (EMT), cell migration, synthesis of alpha smooth muscle actin, contraction and production of extracellular matrix in anterior and posterior lens tissue [4,5,6,7,8,9,10,11,12,13,14,15,16,17,18]
Myo/Nog cells, which exist at low frequency in many tissues, are identified by their expression of mRNA for the skeletal muscle specific transcription factor MyoD, the bone morphogenetic protein (BMP) inhibitor Noggin and the cell surface molecule recognized by the G8 monoclonal antibody [20,21,23,24,25,26,27]
Summary
Posterior capsule opacification (PCO) is a vision impairing condition that arises in some patients following cataract surgery [1,2]. Visual acuity is compromised by the formation of Elschnig pearls that consist of differentiating lens cells (regenerative PCO) and the emergence of myofibroblasts that migrate onto the lens capsule and deposit extracellular matrix (fibrotic PCO) [3]. Several families of molecules have been implicated in the emergence of myofibroblasts in lens tissue [43], including transforming growth factor beta (TGF-b) that induces an epithelial to mesenchymal transition (EMT), cell migration, synthesis of alpha smooth muscle actin (aSMA), contraction and production of extracellular matrix in anterior and posterior lens tissue [4,5,6,7,8,9,10,11,12,13,14,15,16,17,18]. Depletion of Myo/Nog cells in the blastocyst results in severe malformations of the body wall, central nervous system and the eyes due to deregulated BMP signaling [20,21,26]
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