<scp>M</scp>yo/<scp>N</scp>og cells in normal, wounded and tumor‐bearing skin

Gerhart, Jacquelyn; Hayes, Candace S.; Scheinfeld, Victoria; Chernick, Michael R.; George‐Weinstein, Mindy; Gilmour, Susan K.

doi:10.1111/j.1600-0625.2012.01503.x

Cited by 16 publications

(48 citation statements)

References 29 publications

(27 reference statements)

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“…The following anti-sense sequences were conjugated to 3DNA: human MyoD1 (NM_002478.4∶5′-CTGTCCGGCCTGATTTGT GGTTAAGGA-3′) and mouse Noggin (NM_008711.2∶5′-TCTCGTTCAGATCC TTCTCCTTAGGGTCAAA-3′) [34], [35]. The sequence to mouse Noggin was 94% homologous to human Noggin (29 out of 31 bases) [36] and showed the same co-localization pattern with the G8 mAb in murine and human tissues [27].…”

Section: Methodsmentioning

confidence: 99%

Myo/Nog Cells: Targets for Preventing the Accumulation of Skeletal Muscle-Like Cells in the Human Lens

et al. 2014

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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.

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Section: Methodsmentioning

confidence: 99%

Myo/Nog Cells: Targets for Preventing the Accumulation of Skeletal Muscle-Like Cells in the Human Lens

et al. 2014

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“…Myo/Nog cells are also present in adult tissues, including the human eye (Gerhart et al, 2012(Gerhart et al, , 2014Bravo-Nuevo et al, 2015;Brandli et al, 2017). In anterior human lens tissue removed during cataract surgery, Myo/Nog cells synthesize skeletal muscle sarcomeric proteins and surround wrinkles in the capsule denuded of epithelial cells (Gerhart et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Antibody-Conjugated, DNA-Based Nanocarriers Intercalated with Doxorubicin Eliminate Myofibroblasts in Explants of Human Lens Tissue

Gerhart

Greenbaum

Casta

et al. 2017

J Pharmacol Exp Ther

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Posterior capsule opacification (PCO) occurs in some adults and most children following cataract surgery. The fibrotic form of PCO arises, in part, from migratory, contractile myofibroblasts that deform the lens capsule and impair vision. In short-term cultures of human anterior lens tissue, myofibroblasts emerge from Myo/Nog cells that are identified with the G8 monoclonal antibody and by their expression of the MyoD transcription factor and bone morphogenetic protein inhibitor noggin. In this study, we tested the hypothesis that targeted depletion of Myo/Nog cells with the G8 monoclonal antibody (mAb) conjugated to three-dimensional DNA nanocarriers intercalated with doxorubicin (G8:3DNA:Dox) would prevent the accumulation of myofibroblasts in long-term, serum- and growth factor-free cultures of human lens tissue obtained by capsulorhexis. The mAb:nanocarrier complex was internalized into acidic compartments of the cell. G8:3DNA:Dox killed nearly all Myo/Nog cells without affecting the lens epithelial cells. In 30-day cultures, all G8-positive cells expressed noggin, and subpopulations had synthesized MyoD, sarcomeric myosin, and alpha smooth muscle actin (-SMA). Myo/Nog cells responded to scratching of the lens epithelium by accumulating around the edges of the wound. Treatment with two doses of G8:3DNA:Dox completely eliminated G8+/-SMA+ cells throughout the explant. These experiments demonstrate that Myo/Nog cells are the source of myofibroblasts in long-term cultures of anterior human lens tissue and mAb:3DNA nanocarriers specifically and effectively deliver cytotoxic cargo to a subpopulation of cells without off-target effects. G8:3DNA:Dox has the potential to reduce PCO following cataract surgery.

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“…24,28,30 Myo/Nog cells also react to wounding in the embryo and adult. [30][31][32][33][34][35][36][37] Within 24 hours of epidermal abrasion, Myo/Nog cells increase in number and populate the wound. 38 In the retina, the Myo/Nog population expands in response to hypoxia and damaging levels of light.…”

mentioning

confidence: 99%

Depletion of Myo/Nog Cells in the Lens Mitigates Posterior Capsule Opacification in Rabbits

Gerhart

Werner

Mamalis

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Posterior capsule opacification (PCO) is a vision-impairing disease that occurs in some adults and most children after cataract surgery. Contractile myofibroblasts contribute to PCO by producing wrinkles in the lens capsule that scatter light. Myofibroblasts in the lens originate from Myo/Nog cells named for their expression of the MyoD transcription factor and bone morphogenetic protein inhibitor noggin. In this study we tested the effects of depleting Myo/Nog cells on development of PCO. METHODS. Myo/Nog cells were eliminated by injecting the G8 antibody conjugated to 3DNA nanocarriers for the cytotoxin doxorubicin (G8:3DNA:Dox) during cataract surgery in rabbits. The severity of PCO was scored by slit lamp analysis, gross and histologic observation, and immunofluorescence localization of a-smooth muscle actin. RESULTS. G8:3DNA:Dox specifically induced cell death in Myo/Nog cells in the lens. None of the lenses administered G8:3DNA containing 9 to 36 lM doxorubicin developed greater than trace levels of central PCO and few myofibroblasts were present on the capsule. Less than 9% of these lenses exhibited greater than mild levels of peripheral PCO. Doxorubucin itself reduced PCO; however, myofibroblasts and wrinkles were abundant in the lens, and off-target effects were observed in the ciliary processes and cornea. CONCLUSIONS. Myo/Nog cells are the primary source of myofibroblasts in the lens after cataract surgery. Targeted depletion of Myo/Nog cells has potential for preventing PCO and preserving vision.

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Myo/Nog cells in normal, wounded and tumor‐bearing skin

Cited by 16 publications

References 29 publications

Myo/Nog Cells: Targets for Preventing the Accumulation of Skeletal Muscle-Like Cells in the Human Lens

Myo/Nog Cells: Targets for Preventing the Accumulation of Skeletal Muscle-Like Cells in the Human Lens

Antibody-Conjugated, DNA-Based Nanocarriers Intercalated with Doxorubicin Eliminate Myofibroblasts in Explants of Human Lens Tissue

Depletion of Myo/Nog Cells in the Lens Mitigates Posterior Capsule Opacification in Rabbits

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