Role of Caveolin-1 for Blocking the Epithelial-Mesenchymal Transition in Proliferative Vitreoretinopathy

Abstract

PURPOSE. Proliferative vitreoretinopathy (PVR) is one of the most severe ocular diseases. Fibrotic changes in retinal cells are considered to be involved in the pathogenesis of PVR. Epithelial-mesenchymal transition (EMT) of RPE cells is one of the main concepts in the pathogenesis of fibrovascular membranes (FVMs) in PVR. In this study, we examined the expression of Caveolin-1 in human FVMs from patients with PVR. We also examined the role of Caveolin-1 in the pathogenesis of PVR.METHODS. Western blotting, real-time PCR, and immunohistochemistry were performed with human FVMs and mouse eyes with PVR. Cell migration assays were performed to evaluate the involvement of Caveolin-1 in EMT using primary human and mouse RPE cells. RESULTS.Caveolin-1 was expressed in human FVMs and upregulated in the mouse eyes with PVR. The alpha-smooth muscle actin (aSMA) expression and migration ability were increased in RPE cells with knockout or knockdown of Caveolin-1, whereas zonula occludens-1 (ZO-1) immunohistochemistry showed reduced morphology and expression of ZO-1. In addition, migration assays showed that Caveolin-1 reduction increased RPE cell migration abilities.CONCLUSIONS. These results indicated that Caveolin-1 in RPE cells prevents PVR by blocking EMT.

Role of Caveolin-1 in Diabetes and Its Complications

“…CAV1 was recently found highly expressed in the proliferative membranes of mice eyes with PVR, and CAV1 reduction increased retinal pigment epithelium cell migration abilities. This indicates that CAV1 might be a potential therapeutic target in preventing proliferative membrane development in PVR [162].…”

“…CAV1 constitutes a part of the rod cell outer segment, hence the possible role of CAV1 in ocular diseases [162]. In the retina, caveolar transcytosis and size were upregulated in streptozotocin-(STZ-) induced diabetic rats [10].…”

In Vitro Epiretinal Membrane Model and Antibody Permeability: Relationship With Anti-VEGF Resistance in Diabetic Macular Edema

“…The tissue was immediately fixed with 4% paraformaldehyde and cryoprotected; then, 10-lm sections were obtained, as previously described. 33,34 The sections were stained with hematoxylin and eosin, or immunostained with anti-alpha smooth muscle actin (aSMA) antibody (1:200; Sigma-Aldrich, St. Louis, MO, USA), anti-glial fibrillary acidic protein (GFAP) antibody (1:400; Cell Signaling Technology, Danvers, MA, USA), and anti-collagen type I antibody (1:200; Rockland Immunochemicals, Inc., Limerick, PA, USA); they were then visualized with Alexa 488-and Alexa 594-conjugated antibodies (1:1000; Invitrogen, Carlsbad, CA, USA), as well as 4 0 , 6diamidino-2-phenylindole (DAPI; Invitrogen). Images were acquired with a BioImaging Navigator fluorescence microscope (BZ-9000; Keyence, Osaka, Japan).…”

Cytokine profiling in the sub-silicone oil fluid after vitrectomy surgeries for refractory retinal diseases

“…IL-12 plays a certain role in the pathogenesis of idiopathic lung fibrosis (IPF) by regulating the Th-1 cell action 21 . Based on the biological studies suggesting that PVR and idiopathic lung fibrosis have many biological reactions in common 22, 23 , IL-12p40 possibly plays a certain role in the pathogenesis of PVR by regulating the T-helper cell action. IL-6 is one of the major pro-inflammatory cytokines, but it has also been reported to be a photoreceptor neuroprotectant in the experimental model of RD 24 .…”