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.

Keywords: epithelial-mesenchymal transition; microRNA; proliferative vitreoretinopathy; retinal detachment; retinal pigment epithelium.

Figure 1

Illustration of pathogenesis of PVR. In eyes with RD (left), floating RPE cells receive certain biological signals, induce epithelial–mesenchymal transition, and RPE-derived fibrotic cells migrate on the surface of the retina. Color fundus image of PVR (right) showing wrinkling of the retinal surface, retinal stiffness, vessel tortuosity, and subretinal strands. The white arrow indicates a retinal break, and the white arrowheads indicate detached retina. The yellow filled arrowheads indicate wrinkling of the retinal surface, and yellow open arrowheads indicate epiretinal fibrotic membranes.

Figure 2

Growth of the number of microRNA-related publications. PubMed entries that reference the term “microRNA” are represented by the blue bars, those that reference “microRNA” AND “eye” are represented by the red line, and those that reference “microRNA” AND “retina” are represented by the green line.

Figure 3

Correlation between microRNA expression and inflammatory cytokines. (A) miR-148a expression in eyes with RD was significantly correlated with FGF-2, but not with IFN-γ, IL-10, IL-12p40, IL-1β, IL-6, IL-8, MCP-1, TNFα, and VEGF. (B) FGF-2 levels that was secreted in the medium from hRPE cells transfected with miR148_mimic did not show significant difference from those with control microRNA (n = 12, P = 0.54).

Figure 4

Caveolin-1 expression is altered by miR-199, but not by miR-148a. Shown is a comparison of caveolin-1 expressions in primary human RPE cells after being transfected with miR148-mimic versus control microRNA (miR_Ctrl) and with miR199-mimic versus control microRNA (miR_Ctrl). Caveolin-1 is suppressed by miR-199, but not by miR-148a.