Myo/Nog cells are nonprofessional phagocytes.

Myo/Nog cells were discovered in the chick embryo epiblast. Their expression of MyoD reflects a commitment to the skeletal muscle lineage and capacity to differentiate into myofibroblasts. Release of Noggin by Myo/Nog cells is essential for normal morphogenesis. Myo/Nog cells rapidly respond to wounding in the skin and eyes. In this report, we present evidence suggesting that Myo/Nog cells phagocytose tattoo ink in tissue sections of human skin and engulf cell corpses in cultures of anterior human lens tissue and magnetic beads injected into the anterior chamber of mice in vivo. Myo/Nog cells are distinct from macrophages in the skin and eyes indicated by the absence of labeling with an antibody to ionized calcium binding adaptor molecule 1. In addition to their primary roles as regulators of BMP signaling and progenitors of myofibroblasts, Myo/Nog cells behave as nonprofessional phagocytes defined as cells whose primary functions are unrelated to phagocytosis but are capable of engulfment.

Brain-specific angiogenesis inhibitor 1 is expressed in the Myo/Nog cell lineage.

The Myo/Nog cell lineage was discovered in the chick embryo and is also present in adult mammalian tissues. The cells are named for their expression of mRNA for the skeletal muscle specific transcription factor MyoD and bone morphogenetic protein inhibitor Noggin. A third marker for Myo/Nog cells is the cell surface molecule recognized by the G8 monoclonal antibody (mAb). G8 has been used to detect, track, isolate and kill Myo/Nog cells. In this study, we screened a membrane proteome array for the target of the G8 mAb. The array consisted of >5,000 molecules, each synthesized in their native confirmation with appropriate post-translational modifications in a single clone of HEK-293T cells. G8 mAb binding to the clone expressing brain-specific angiogenesis inhibitor 1 (BAI1) was detected by flow cytometry, re-verified by sequencing and validated by transfection with the plasmid construct for BAI1. Further validation of the G8 target was provided by enzyme-linked immunosorbent assay. The G8 epitope was identified by screening a high-throughput, site directed mutagenesis library designed to cover 95-100% of the 954 amino acids of the extracellular domain of the BAI1 protein. The G8 mAb binds within the third thrombospondin repeat of the extracellular domain of human BAI1. Immunofluorescence localization experiments revealed that G8 and a commercially available BAI1 mAb co-localize to the subpopulation of Myo/Nog cells in the skin, eyes and brain. Expression of the multi-functional BAI1 protein in Myo/Nog cells introduces new possibilities for the roles of Myo/Nog cells in normal and diseased tissues.

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

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 α-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 µM 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.

Myo/Nog cells are present in the ciliary processes, on the zonule of Zinn and posterior capsule of the lens following cataract surgery.

Myo/Nog cells, named for their expression of MyoD and noggin, enter the eye during early stages of embryonic development. Their release of noggin is critical for normal morphogenesis of the lens and retina. Myo/Nog cells are also present in adult eyes. Single nucleated skeletal muscle cells designated as myofibroblasts arise from Myo/Nog cells in cultures of lens tissue. In this report we document the presence of Myo/Nog cells in the lens, ciliary body and on the zonule of Zinn in mice, rabbits and humans. Myo/Nog cells were rare in all three structures. Their prevalence increased in the lens and ciliary body of rabbits 24 h following cataract surgery. Rabbits developed posterior capsule opacification (PCO) within one month of surgery. The number of Myo/Nog cells continued to be elevated in the lens and ciliary body. Myo/Nog cells containing alpha smooth muscle actin and striated muscle myosin were present on the posterior capsule and overlaid deformations in the capsule. Myo/Nog cells also were present on the zonule fibers and external surface of the posterior capsule. These findings suggest that Myo/Nog contribute to PCO and may use the zonule fibers to migrate between the ciliary processes and lens.