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

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.

Keywords: FGF; TGF β; epithelial-mesenchymal transition; lens epithelium-cell derived growth factor; peroxiredoxin 6; reactive oxygen species; tropomyosin.

Figure 1

Changes in LECs observed in PCO. After cataract surgery, residual LECs induce cell proliferation, migration, EMT, collagen deposition and regeneration of lens fibers causing PCO, or so-called secondary cataracts.

Figure 2

PCO and cataracts with Anterior subcapsular fibrosis (ASF). (A) Slit-lamp retroillumination photos of PCO development. PCO is the most common complication of cataract surgery. It is caused by the migration of residual LECs from the equatorial region of the lens capsule. (B) A slit-lamp image of a cataract with ASF. Cataracts with ASF are usually seen at the anterior pole of the lens. Fibroblastic LECs are observed in this portion.

Figure 3

Overview of EMT and EMyoT induction in LECs by TGF β2 and FGF2. TGFβ induces EMyoT and Tpm expression. Tpms promote the formation of stress fibers undergoing EMyoT. FGF2 suppresses the TGFβ2-induced over-expression of Tpms. Depletion of Tpms by FGF suppresses the formation of stress fibers and activates fibroblastic LECs, which lose cell polarity, inducing cell migration.