Myo/Nog cells expressing muscle proteins are present in preretinal membranes from patients with proliferative vitreoretinopathy

Gerhart, Jacquelyn; Morrison, Nathan; Gugerty, Lindsay; Telander, David G.; Bravo‐Nuevo, Arturo; George‐Weinstein, Mindy

doi:10.1016/j.exer.2020.108080

Cited by 6 publications

(17 citation statements)

References 36 publications

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“…4 , 5 , 13 , 16 – 22 Our analyses of human ERMs obtained from patients with a previous rhegmatogenous retinal detachment revealed that alpha smooth muscle actin (α-SMA), striated muscle myosin, and the skeletal muscle specific transcription factor myoblast determination factor 1 (MyoD) were exclusively expressed in a subpopulation called Myo/Nog cells. 23 The presence of differentiated Myo/Nog cells in human PVR membranes is consistent with the results of Shirpa et al 24 who found a significant elevation of another member of the MyoD family, myogenic factor 6 (Myf6), in the vitreous of patients with rhegmatogenous retinal detachment compared to those with a macular hole and pucker.…”

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confidence: 87%

Myo/Nog Cells Give Rise to Myofibroblasts During Epiretinal Membrane Formation in a Mouse Model of Proliferative Vitreoretinopathy

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Gerhart

Heffer

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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Purpose Myo/Nog cells are the source of myofibroblasts in the lens and synthesize muscle proteins in human epiretinal membranes (ERMs). In the current study, we examined the response of Myo/Nog cells during ERM formation in a mouse model of proliferative vitreoretinopathy (PVR). Methods PVR was induced by intravitreal injections of gas and ARPE-19 cells. PVR grade was scored by fundus imaging, optical coherence tomography, and histology. Double label immunofluorescence localization was performed to quantify Myo/Nog cells, myofibroblasts, and leukocytes. Results Myo/Nog cells, identified by co-labeling with antibodies to brain-specific angiogenesis inhibitor 1 (BAI1) and Noggin, increased throughout the eye with induction of PVR and disease progression. They were present on the inner surface of the retina in grades 1/2 PVR and were the largest subpopulation of cells in grades 3 to 6 ERMs. All α-SMA-positive (+) cells and all but one striated myosin+ cell expressed BAI1 in grades 1 to 6 PVR. Folds and areas of retinal detachment were overlain by Myo/Nog cells containing muscle proteins. Low numbers of CD18, CD68, and CD45+ leukocytes were detected throughout the eye. Small subpopulations of BAI1+ cells expressed leukocyte markers. ARPE-19 cells were found in the vitreous but were rare in ERMs. Pigmented cells lacking Myo/Nog and muscle cell markers were present in ERMs and abundant within the retina by grade 5/6. Conclusions Myo/Nog cells differentiate into myofibroblasts that appear to contract and produce retinal folds and detachment. Targeting BAI1 for Myo/Nog cell depletion may be a pharmacological approach to preventing and treating PVR.

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confidence: 87%

Myo/Nog Cells Give Rise to Myofibroblasts During Epiretinal Membrane Formation in a Mouse Model of Proliferative Vitreoretinopathy

Crispin

Gerhart

Heffer

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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“…With state-of-the-art quantitative mass spectrometry, that is, a data-independent acquisition (DIA) method using SWATH-MS proteomics technique, we quantified 1177 proteins. Interestingly, RRD patients had 178 times higher vitreal content of myogenic factor 6 (Myf6 or MRF4) compared with the neurodegenerative vitreoretinal eye diseases macular hole and pucker (Welch's t-test, q = 0. of Myo/Nog cell markers and muscle proteins in PVR membranes, providing further evidence on involvement of an inherently myogenic cell type in the PVR disease process in RRD eyes (Gerhart et al 2020;€ Ohman et al 2021). Understanding processes related to cell proliferation, tissue remodelling and scar tissue formation in RRD is of great importance.…”

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confidence: 93%

Vitreal protein myogenic factor 6 is increased in eyes with rhegmatogenous retinal detachment

Loukovaara

Korhonen

Varjosalo

et al. 2022

Acta Ophthalmologica

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“…Myo/Nog cells differentiate into myofibroblasts in the lens and they synthesize skeletal muscle proteins in human preretinal membranes (Gerhart et al, 2014(Gerhart et al, , 2017(Gerhart et al, , 2019b(Gerhart et al, , 2020c. Vanlandewijck et al (2018) surveyed the whole brain and found two types of fibroblast-like cells.…”

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confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Neonatal and adult tissues also contain Myo/Nog cells where they are present in low numbers until activated by injury (Walker et al, 2010;Gerhart et al, 2012Gerhart et al, , 2014Gerhart et al, , 2018Gerhart et al, , 2019bGerhart et al, , 2020cBrandli et al, 2017). They are the source of contractile myofibroblasts in the lens and synthesize skeletal muscle proteins in human preretinal membranes (Gerhart et al, 2014(Gerhart et al, , 2017(Gerhart et al, , 2019b(Gerhart et al, , 2020c. Myo/Nog cells lack detectable levels of NeuN, glial fibrillary acid protein and markers of microglia in the mouse brain and retinas of mice and rats (Bravo-Nuevo et al, 2016;Brandli et al, 2017;Gerhart et al, 2020a), although like microglia, they engage in phagocytosis (Gerhart et al, 2020b).…”

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confidence: 99%

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Acute Response and Neuroprotective Role of Myo/Nog Cells Assessed in a Rat Model of Focal Brain Injury

et al. 2021

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Focal brain injury in the form of a needlestick (NS) results in cell death and induces a self-protective response flanking the lesion. Myo/Nog cells are identified by their expression of bone morphogenetic protein inhibitor Noggin, brain-specific angiogenesis inhibitor 1 (BAI1) and the skeletal muscle specific transcription factor MyoD. Myo/Nog cells limit cell death in two forms of retinopathy. In this study, we examined the acute response of Myo/Nog cells to a NS lesion that extended from the rat posterior parietal cortex to the hippocampus. Myo/Nog cells were identified with antibodies to Noggin and BAI1. These cells were the primary source of both molecules in the uninjured and injured brain. One day after the NS, the normally small population of Myo/Nog cells expanded approximately eightfold within a 1 mm area surrounding the lesion. Myo/Nog cells were reduced by approximately 50% along the lesion with an injection of the BAI1 monoclonal antibody and complement. The number of dying cells, identified by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), was unchanged at this early time point in response to the decrease in Myo/Nog cells. However, increasing the number of Myo/Nog cells within the lesion by injecting BAI1-positive (+) cells isolated from the brains of other animals, significantly reduced cell death and increased the number of NeuN+ neurons compared to brains injected with phosphate buffered saline or exogenous BAI1-negative cells. These findings demonstrate that Myo/Nog cells rapidly react to injury within the brain and increasing their number within the lesion is neuroprotective.

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Myo/Nog cells expressing muscle proteins are present in preretinal membranes from patients with proliferative vitreoretinopathy

Cited by 6 publications

References 36 publications

Myo/Nog Cells Give Rise to Myofibroblasts During Epiretinal Membrane Formation in a Mouse Model of Proliferative Vitreoretinopathy

Myo/Nog Cells Give Rise to Myofibroblasts During Epiretinal Membrane Formation in a Mouse Model of Proliferative Vitreoretinopathy

Vitreal protein myogenic factor 6 is increased in eyes with rhegmatogenous retinal detachment

Acute Response and Neuroprotective Role of Myo/Nog Cells Assessed in a Rat Model of Focal Brain Injury

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