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Linda Musil; Dual function of TGFβ in lens cell fate: implications for PCO. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Posterior capsule opacification is caused by lens cells undergoing two very different fates after cataract surgery: conversion to myofibroblastic cells, and differentiation into lens fiber-like cells. Although TGFβ has long been associated with the etiology of fibrotic PCO, the causes of lens fiber-type PCO are less established. It is also not known what determines whether a lens cell undergoes one cell fate or the other. We reported that adding TGFβ to primary cultures of chick lens epithelial cells (DCDMLs) induces some cells to undergo epithelial-mesenchymal transition (EMT) to myofibroblasts, and others to become lens fiber-like cells. Alteration of intrinsic kinase signaling can induce TGFβ-treated DCDMLs to preferentially adopt one cell fate or the other. Here, we report that cell-extrinsic factors can also profoundly affect lens cell differentiation in response to TGFβ.
Expression of markers of EMT and lens fiber differentiation in DCDMLs was assessed by Western blotting, metabolic labeling, or immunocytochemistry, and signaling pathways measured using phospho-specific antibodies.
We found that low cell density cultures responded to TGFβ by overwhelmingly undergoing EMT, whereas addition of TGFβ to cultures at near confluent density induced lens fiber cell differentiation but little expression of markers of EMT. Other experiments revealed that increasing the volume of medium by > 2-fold greatly increased the number of myofibroblasts after a 7 day treatment with TGFβ. The latter effect was related to the ability of lens cells to condition their medium in a manner that prevents TGFβ from inducing EMT without inhibiting lens fiber differentiation.
These results could help explain why shortly after cataract surgery, fibrosis occurs predominantly on the anterior of the lens capsule. In contrast, lens epithelial cells near the former equator of the lens (where the area bordered by the anterior and posterior capsules and the IOL optic creates a restricted, low volume space) would have a greater tendency to differentiate into lens fiber cells to form Soemmering's Ring, considered to be a source of Elschnig pearls. Understanding how cell density and medium volume influence lens cell fate could lead to new approaches to prevent capsule opacification. Our findings could also shed light on results obtained in other PCO model systems.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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