title: Myo/Nog cells: targets for preventing the accumulation of skeletal muscle-like cells in the human lens.
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.
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, Pennsylvania, United States of America.
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Gerhart
authors.affiliation: Lankenau Medical Center, Wynnewood, Pennsylvania, United States of America.
authors.forename: Marvin
authors.initials: M
authors.lastname: Greenbaum
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, Pennsylvania, United States of America.
authors.forename: Victoria
authors.initials: V
authors.lastname: Scheinfeld
authors.affiliation: Department of Cell Biology and Human Anatomy, School of Medicine, University of California Davis, Davis, California, United States of America.
authors.forename: Paul
authors.initials: P
authors.lastname: Fitzgerald
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, Pennsylvania, United States of America.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Crawford
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, Pennsylvania, United States of America.
authors.forename: Arturo
authors.initials: A
authors.lastname: Bravo-Nuevo
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, Pennsylvania, United States of America.
authors.forename: Meghan
authors.initials: M
authors.lastname: Pitts
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, Pennsylvania, United States of America.
authors.forename: Mindy
authors.initials: M
authors.lastname: George-Weinstein
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D019923:Capsulorhexis / Q000009:adverse effects*; D002352:Carrier Proteins / Q000378:metabolism*; D002452:Cell Count; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology*; D017570:MyoD Protein / Q000378:metabolism*; D058628:Myofibroblasts / Q000166:cytology* / Q000378:metabolism*; D000099176:Noggin Protein
chemical_list: D002352:Carrier Proteins; D009124:Muscle Proteins; D017570:MyoD Protein; D000099176:Noggin Protein
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