Abstract
The epithelial–mesenchymal transition (EMT) is a common feature of disease progression in diseases such as cancer and fibrosis. It is associated with the enhanced migration and proliferation of cells and the synthesis and secretion of extracellular matrix (ECM) molecules. Proliferative vitreoretinopathy (PVR) arises in the eye through the occurrence of EMT in retinal pigment epithelium (RPE) cells that have become dislodged from the blood-retinal barrier, following retinal detachment after ocular trauma. These dislodged cells undergo EMT to form contractile membranous tissues called epiretinal membranes (ERMs) in the vitreous humor, and cause tractional retinal detachment and vision loss even after retinal reattachment surgery. We have previously developed a cell culture-based model simulating retinal cell EMT (RC-EMT) in which RPE cells are exposed to vitreous humor and subretinal fluid (PVS) from patients subjected to vitrectomy. Here, we present a detailed proteomics-based examination of our cell culture-based model which establishes that the exposure of RPE cells to PVS activates biological processes/pathways associated with EMT. Our study throws light on the sequence of progression of events in retinal cell EMT; in particular, we find the expression of fibronectin to be significantly upregulated before the appearance of morphological changes associated with fibrosis. The study thus shows the cell culture-based model to be a physiologically relevant mimic of EMT associated with PVR pathogenesis that can help in screening, discovery and testing of therapeutics for EMT-related pathologies.
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The work was funded by grant given to MLG by the Science and Engineering Research Board (SERB), Department of Science and Technology, Government of India (Grant No: EMR/2014/001164).
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MS and MLG designed the study. SS and AKT collected data. DK, RB, RS, MRD provided the patient materials. AKT and MLG performed the analysis, designed the figures, interpreted the results. MLG supervised the work, got the funding and wrote the manuscript.
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The study was conducted in accordance with the tenets of the Declaration of Helsinki and was approved by the Institutional Ethics Committee of Postgraduate Institute of Medical Education and Research (PGIMER).
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Sharma, S., Thakur, A.K., Sharma, M. et al. A simulacrum of proliferative vitreoretinopathy (PVR): development and proteomics-based validation of an in vitro model. J Proteins Proteom (2024). https://doi.org/10.1007/s42485-024-00140-0
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DOI: https://doi.org/10.1007/s42485-024-00140-0