Transforming growth factor‐β₁ induces α‐smooth muscle actin expression and fibronectin synthesis in cultured human retinal pigment epithelial cells

Abstract

Elevated levels of TGF-beta1 in proliferative vitreoretinopathy may contribute to phenotype changes in retinal pigment epithelial cells leading to matrix deposition and contraction. Since the elevated levels of TGF-beta1 may emanate from a number of diverse sources in proliferative vitreoretinopathy, developing an antagonist to TGF-beta1 may offer an approach to the treatment of proliferative vitreoretinopathy.

Smad3 is required for dedifferentiation of retinal pigment epithelium following retinal detachment in mice

“…Primary porcine RPE cells express aSMA when cultured in the presence of TGF-b2 ( Figure 4bB), but not in its absence (Figure 4bA), in agreement with that shown previously. 5 Similar to that shown for primary human RPE cells, 19 a human RPE cell line, ARPE-19, 34 also exhibited a morphological change to a more fibroblastic appearance (Figure 4cB) and showed clusters of aSMA-positive cells after treatment with TGF-b2 for 72 h (Figure 4cD) as compared with cells incubated without TGF-b2 (Figure 4cA, C). These data strongly suggest that the aSMA-positive cells in the retinal detachment model in vivo likely arise by EMT of RPEs.…”

“…Since the histology was suggestive of perturbed EMT, or fibroblastic dedifferentiation of RPE cells in KO eyes in response to retinal detachment, we examined whether expression of aSMA, that is considered to be a hallmark of EMT and of acquisition of a myofibroblast phenotype 5,18,19,47 would also be reduced or absent in KO eyes. Regardless of the genotype, no aSMA protein was detected in uninjured RPE cells or in the first few days postretinal detachment (Figure 2a, b).…”

“…[13][14][15][16] TGF-b2 is expressed at much higher levels than the other TGF-b isoforms in the vitreous humor 12,17 and is a likely mediator of EMT in RPE cells in vivo, although the specific signaling pathways involved have not been identified. 5,18,19 Moreover, PDGF, TGF-b1 and CTGF are each known to be targets of TGF-b2 signaling, [20][21][22][23] suggesting that TGFb2 could orchestrate the secondary effects of these other peptides on EMT and fibrosis in PVR.…”

Effect of Tranilast on Proliferation, Collagen Gel Contraction, and Transforming Growth Factor Beta Secretion of Retinal Pigment Epithelial Cells and Fibroblasts

“…It is likely that TGF-ß 1 and TGF-ß 2 also directly facilitate differentiation of RPE cells to myofibroblasts [43,46]. Thus, RPE cells had the capabilities of fibroblasts and secreted extracellular matrix, chemokines such as interleukin-8, and growth factors including TGF-ß [46,47].…”

Myofibroblast transdifferentiation: The dark force in ocular wound healing and fibrosis

“…Moreover, the TGFβ2 isoform and its receptor (TGFβ-RII) have been identified within excised human PVR membranes (Cui et al, 2007). Numerous studies have shown that TGFβ induces myofibroblast transdifferentiation in RPE cells in human (Stocks et al, 2001; Li et al, 2011; Xiao et al, 2014; Dvashi et al, 2015) and murine models (Saika et al, 2004b; Saika et al, 2007) of PVR.…”