PURPOSE. Fibroblast growth factor (FGF) plays a key role in normal lens biology, and recent studies suggest that transforming growth factor (TGF)- is involved in the origin of certain forms of cataract. In the current study, the effects of FGF and TGF on ␣A-crystallin promoter activity were investigated. METHODS. Rat lens epithelial explants were cultured with or without growth factors after transfecting with the firefly luciferase reporter gene driven by either the mouse ␣A-crystallin promoter region or a control simian virus (SV)40 promoter. RESULTS. FGF-2, at a concentration that induced lens fiber differentiation, strongly stimulated ␣A-crystallin promoter activity in explants at 3 to 4 days of culture, whereas SV40 promoter control specimens showed no comparable increase. At lower concentrations of FGF, sufficient to induce cell proliferation but not differentiation, there was only a slight increase in ␣A-crystallin promoter activity. Stimulation of ␣A-crystallin promoter activity induced by the fiber-differentiating concentration of FGF was virtually abolished by as little as 25 pg/ml TGF2, but the onset of fiber-specific -crystallin accumulation was not prevented at this concentration. Phase-contrast microscopy revealed overt cataractous changes only at concentrations of TGF more than 25 pg/ml. CONCLUSIONS. The stimulation of ␣A-crystallin promoter activity by FGF is consistent with its role in inducing accumulation of crystallins in explants. The blocking effect of TGF on this process, even at a concentration too low to induce obvious pathologic changes, indicates the potential for TGF to disturb ␣A-crystallin gene expression during early fiber differentiation. (Invest Ophthalmol Vis Sci
