Roles of TGF β and FGF Signals in the Lens: Tropomyosin Regulation for Posterior Capsule Opacity.

Eri Kubo,Teppei Shibata,Hiroshi Sasaki,Dhirendra Singh

doi:10.3390/ijms19103093

Eri Kubo, Teppei Shibata + Show 2 more

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https://doi.org/10.3390/ijms19103093

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Abstract

Transforming growth factor (TGF) β and fibroblast growth factor (FGF) 2 are related to the development of posterior capsule opacification (PCO) after lens extraction surgery and other processes of epithelial–mesenchymal transition (EMT). Oxidative stress seems to activate TGF β1 largely through reactive oxygen species (ROS) production, which in turn alters the transcription of several survival genes, including lens epithelium-cell derived growth factor (LEDGF). Higher ROS levels attenuate LEDGF function, leading to down-regulation of peroxiredoxin 6 (Prdx6). TGF β is regulated by ROS in Prdx6 knock-out lens epithelial cells (LECs) and induces the up-regulation of tropomyosins (Tpms) 1/2, and EMT of LECs. Mouse and rat PCO are accompanied by elevated expression of Tpm2. Further, the expression of Tpm1/2 is induced by TGF β2 in LECs. Importantly, we previously showed that TGF β2 and FGF2 play regulatory roles in LECs in a contrasting manner. An injury-induced EMT of a mouse lens as a PCO model was attenuated in the absence of Tpm2. In this review, we present findings regarding the roles of TGF β and FGF2 in the differential regulation of EMT in the lens. Tpms may be associated with TGF β2- and FGF2-related EMT and PCO development.

Highlights

The ocular lens is a transparent organ that changes its shape to adjust the focal distance of the eye in order to focus on objects
We propose that clarifying the physiological link between the levels of FGF2, Tpm1 and Tpm2 expression, and transforming growth factor (TGF) β-orchestrated epithelial-to-myofibroblastic transition (EMyoT) may help to develop therapeutic targets based on Tpm1 and Tpm2 to prevent posterior capsular opacification (PCO) (Figure 3)
reactive oxygen species (ROS) up-regulate TGF β-mediated signaling, inducing the aberrant expression of certain genes, including those encoding Tpm1, Tpm2, lens epithelium-derived growth factor (LEDGF), and α smooth muscle actin (αSMA), which are involved in the induction of Epithelial-mesenchymal transition (EMT) in Lens epithelial cells (LECs) [17,35,58]

Summary

Introduction

The ocular lens is a transparent organ that changes its shape to adjust the focal distance of the eye in order to focus on objects. Sci. 2018, 19, 3093; doi:10.3390/ijms19103093 www.mdpi.com/journal/ijms have been observed in lens-specific transgenic mice expressing TGF β1 [12] These changes are found in human cataracts. Oxidative stress induces several functions,TGF including cellular transformation and have been observed in lens-specific transgenic mice expressing β1 [12]. TGF-β-induced genes has been related to cataractogenesis, posterior capsular opacification (PCO), the lens capsule often leads to migration, fibrosis and collagen deposition. This results in secondary and myofibroblast-related disorders [5,9,17]. PCO, which is sometimes referred to ascataract a “secondary orsurgical “after cataract”

[19] (Figures

Tpm2 Knock-Down Reduced Wound Healing of the Mouse Lens In Vivo

Conclusions