Myo/Nog Cells Give Rise to Myofibroblasts During Epiretinal Membrane Formation in a Mouse Model of Proliferative Vitreoretinopathy.
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.
Investigative Ophthalmology & Visual Science
Crispin, Mara; Gerhart, Jacquelyn; Heffer, Alison; Martin, Mark; Abdalla, Fathma; Bravo Nuevo, Arturo; Philp, Nancy J; Kuriyan, Ajay E; and George-Weinstein, Mindy, "Myo/Nog Cells Give Rise to Myofibroblasts During Epiretinal Membrane Formation in a Mouse Model of Proliferative Vitreoretinopathy." (2023). PCOM Scholarly Papers. 2185.
This article was published as the cover article in Investigative Ophthalmology and Visual Science, Volume 64, Issue 2.
The published version is available at https://doi.org/10.1167/iovs.64.2.1.
Copyright © 2023 The Authors. CC BY-NC-ND 4.0.