Experimental Models to Study Epithelial-Mesenchymal Transition in Proliferative Vitreoretinopathy

Abstract

Proliferative vitreoretinal diseases (PVDs) encompass proliferative vitreoretinopathy (PVR), epiretinal membranes, and proliferative diabetic retinopathy. These vision-threatening diseases are characterized by the development of proliferative membranes above, within and/or below the retina following epithelial-mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) and/or endothelial-mesenchymal transition of endothelial cells. As surgical peeling of PVD membranes remains the sole therapeutic option for patients, development of in vitro and in vivo models has become essential to better understand PVD pathogenesis and identify potential therapeutic targets. The in vitro models range from immortalized cell lines to human pluripotent stem-cell-derived RPE and primary cells subjected to various treatments to induce EMT and mimic PVD. In vivo PVR animal models using rabbit, mouse, rat, and swine have mainly been obtained through surgical means to mimic ocular trauma and retinal detachment, and through intravitreal injection of cells or enzymes to induce EMT and investigate cell proliferation and invasion. This review offers a comprehensive overview of the usefulness, advantages, and limitations of the current models available to investigate EMT in PVD.

Silibinin Prevents TGFβ-Induced EMT of RPE in Proliferative Vitreoretinopathy by Inhibiting Stat3 and Smad3 Phosphorylation

“…RPE cell migration is a crucial step in the formation of proliferative membranes in PVR. 27 , 28 During the PVR formation, RPE cells first detach from Bruch's membrane and migrate to the epi-retinal or sub-retinal spaces where they interact with other cellular components and the extracellular matrix to form the proliferative membrane. 7 , 8 In our study, both scratch assay and transwell assay demonstrated that silibinin significantly inhibited the migration of RPE cells.…”

Microfluidic Fabricated Liposomes for Nutlin-3a Ocular Delivery as Potential Candidate for Proliferative Vitreoretinal Diseases Treatment

“…Neovascular age-related macular degeneration (nAMD) also develops membranes, similar to PVDs’ membranes, but the trigger for this pathology mainly consists of inflammation or oxidative stress. 1 …”

“…Neovascular age-related macular degeneration (nAMD) also develops membranes, similar to PVDs' membranes, but the trigger for this pathology mainly consists of inflammation or oxidative stress. 1 It has already been proven that retinal pigment epithelial (RPE) cells are deeply involved in PVDs' development, stimulated by cytokines or growth factors released as a consequence of the trigger events. 2 In particular, RPE cells, that in healthy condition are subjected to contact inhibitory effect and have a very low turnover rate, under a stimulatory event, for example retinal detachment in PVR, improve their proliferative and migratory properties, and undergo morphological changes, losing their cellular polarity and assuming a fibroblastoid appearance, leading to the so-called epithelial-mesenchymal transition (EMT).…”