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.

Role of Myo/Nog Cells in Neuroprotection: Evidence from the Light Damaged Retina

“…Consistent with previous studies in chick, mouse, and human [8, 9, 15], the G8 mAb detected cells that also expressed MyoD and Noggin in the rat retina (Fig 1). In control retinas, G8+ cells were found in low numbers in the OPL (Figs 1F–1H, 2B and 3B), INL (Figs 1B–1H, 2A and 2B) and choroid (Fig 3B).…”

“…Their accumulation near the site of cell death in the rat retina is consistent with the attraction of Myo/Nog cells to sites of injury in the neonatal mouse retina [9]. Myo/Nog cells have also been observed to concentrate at sites of injury in the embryo, skin, lens and tumors [15, 22, 23]. Additional analyses are needed to establish whether the increase in Myo/Nog cells in the stressed retina is due to the proliferation of resident Myo/Nog cells or their migration into the retina from neighboring tissues or the vasculature.…”

“…Noggin is released from Myo/Nog cells during development and in adult tissues, including eyes of humans and mice [1, 3, 8, 9, 15, 22]. This release is critical for morphogenesis, eye development and skeletal muscle differentiation [1, 8].…”

“…Previous studies have shown that Myo/Nog cells in the lens proliferate, migrate to sites of injury, synthesize skeletal muscle proteins and display a myofibroblast phenotype [15, 23]. Additionally, myofibroblasts are present in contractile membranes that can detach the retina in diabetic retinopathy or proliferative vitreoretinopathy[41, 42].…”

Adhesion study of cultured human lens capsule cells on hydrophilic intraocular lenses coated with polyethylene glycol

“…In addition, care was taken to use one half of the cell samples with epithelial morphology and one half with dendritic-like morphology because the latter probably corresponds to epithelial cells undergoing transdifferentiation to activated myofibroblasts which, theoretically, have a higher adhesion capacity. 12,22,23 Two patients in the dendritic-like group were 41 years old and 49 years old, while in the epithelial group all were older than 60 years, Even though the mean age did not differ between both morphology types, this could suggest that younger individuals have a greater chance of developing transdifferentiation to activated myofibroblasts.…”