Biological Involvement of MicroRNAs in Proliferative Vitreoretinopathy

Abstract

Even with a high surgical success rate for retinal detachment and proliferative vitreoretinopathy (PVR) supported by the robust improvement in vitrectomy surgery and its related devices, certain questions still remain for the pathogenesis and treatment of PVR. One of the important biological events in PVR is epithelial–mesenchymal transition (EMT) of the retinal pigment epithelial (RPE) cells. MicroRNAs are noncoding, small, single-strand RNAs that posttranscriptionally regulate gene expression and have essential roles in homeostasis and pathogenesis in many diseases. Recently, microRNAs also had a critical role in EMT in many tissues and cells. One main purpose of this brief review is to describe the knowledge obtained from microRNA research, especially concerning vitreoretinal diseases. In addition, the potential role of microRNAs in prevention of PVR by regulating EMT in RPE cells is described. Understanding microRNA involvement in PVR could be helpful for developing new biological markers or therapeutic targets and reducing the rate of visual disability due to PVR.

Bradykinin B2 Receptor Contributes to Inflammatory Responses in Human Endothelial Cells by the Transactivation of the Fibroblast Growth Factor Receptor FGFR-1

“…Recently, in a model of OIR, in mice, we demonstrated that BK/B2R is involved in the pathological retinal neovascularization and that this effect correlated with upregulation of FGF-2 in retinal vessels [ 22 ]. A limited number of studies suggest the existence of a functional link between the two systems in several inflammatory/angiogenic disorders [ 28 , 29 , 30 ]. Although FGF-2 can trigger neovessel formation per se, the major finding of this study concerns the BK ability to transactivate FGFR-1 signaling in endothelial cells, as evidenced by its phosphorylation and translocation from the plasma membrane to cytosol, and, in turn, by the phosphorylation of second messengers downstream to FGFR-1, as FRSα, ERK1/2, and STAT3.…”

Involvement of Bradykinin B2 Receptor in Pathological Vascularization in Oxygen-Induced Retinopathy in Mice and Rabbit Cornea

“…A limited number of studies suggests that the angiogenic response induced by BK/B2R system could be mediated by the upregulation of proangiogenic factors [ 25 ]. Although evidence for the direct activation of the FGF-2 or VEGF pathway by BK in vivo is not yet available, there is indirect evidence suggesting a functional link between the two systems in several inflammatory diseases, including vasoactive responses [ 17 , 18 , 19 , 20 , 26 ]. Notably, in this study, in the model of OIR, we observed that endothelial cells from retinal vessels express FGF-2 and VEGF, and that fasitibant reduced the expression of both growth factors, also marginally affecting HIF-1α expression.…”

“…FGF-2 stimulates VEGF secretion from vascular smooth muscle, endothelial and Müller cells and synergizes with VEGF in promoting the proliferation of retinal microvascular endothelial cells and pericytes [ 15 , 16 ]. Furthermore, FGF-2 and VEGF levels, as the KKS components, are significantly increased in vitreous from experimental models of retinal diseases [ 17 ], as well as at sites of chronic inflammation [ 18 ], where both growth factors and BK appear to be the key metabolic mediators of inflammatory responses, including vasoactive responses [ 19 , 20 ].…”

Circular and long non-coding RNAs and their role in ophthalmologic diseases

“…Several cell types are associated with the PVR pathogenesis, including retinal pigment epithelial (RPE) cells, fibroblasts, glial cells, and inflammatory cells. RPE cells are the largest cellular component in epiretinal membranes, and, importantly, they undergo dedifferentiation process -epithelial-mesenchymal transition (EMT) -in which they acquire a mesenchymal phenotype (Kaneko & Terasaki, 2017;Yang et al, 2016). This process is the main contributor to PVR progression and involves a number of molecular pathways affecting cell proliferation and migration.…”