FGF-2 counteracts loss of TGFβ affected cells from rat lensexplants: Implications for PCO (after cataract)

[摘要] Purpose: While cataract surgery initially benefits most patients,many suffer secondary loss of vision because of posterior capsuleopacification (PCO). Lens epithelial cells left behind at surgery becomeaberrant and migrate into the light path. TGF-beta (TGFβ) appears toplay a key role in this process by inducing the cells to undergo anepithelial-mesenchymal transition. Paradoxically, it also typicallyinduces them to undergo apoptotic death. The present study wasundertaken to investigate the hypothesis that FGF plays a role in PCOformation by promoting the survival of abnormal cells with PCO-likecharacteristics.Methods: Rat lens epithelial explants were cultured for one day withTGFβ2 (25-100 pg/ml) then in control medium with or without FGF-2(5-100 ng/ml) for up to 31 days, with assessment by light and scanningelectron microscopy and immunolocalization.Results: Survival of TGFβ treated cells was promoted by FGF-2but not by EGF, PDGF, IGF, or HGF. In the absence of FGF virtually allcells were lost from explants within 5 days. However, when FGF wasincluded cells remained viable throughout culture. These cells, which nolonger expressed the lens epithelial marker Pax6, exhibitedimmunoreactivity for non-lens cell proteins associated with PCO(α-smooth muscle actin, type I collagen, and fibronectin) and alsoβ-crystallin. FGF inclusion also promoted ECM production,multilayering, and plaque formation, features of PCO known to contributeto visual loss.Conclusions: This study points to a key role for FGF in the etiologyof PCO and suggests that FGF inhibitors may be useful in preventingPCO.

[学科分类] 生物化学/生物物理