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Abstract
PURPOSE: Previously, using lens epithelial explants from neonatal rats, we showed that both insulin and IGF-1 synergistically enhance the effectiveness of FGF as an inducer of fiber differentiation. The authors aimed to determine whether IGF-1 enhances FGF-induced fiber differentiation in lens epithelial cells at various ages and, in particular, whether it can counter a marked age-related decline in responsiveness to FGF noted previously. METHODS: The effects of IGF-1 and bFGF were assessed using lens epithelial explants from neonatal, weanling, and adult rats. Fiber differentiation (after 13 days' culture) was monitored by crystallin ELISAs of explant lysates and also by immunofluorescent localization of crystallins. RESULTS: IGF alone had minimal effects. For younger rats, FGF alone enhanced the accumulation of alpha-, beta- and gamma-crystallins throughout explants, the peripheral region being more responsive than the central region. For adult rats, only the peripheral region responded; small amounts of alpha- and beta-crystallins were detected, but gamma-crystallin was not. Combining IGF with FGF induced gamma-crystallin in explants from adult rats (peripheral region) and enhanced the accumulation of all crystallins more than additively at all ages, mainly in the central region (young rats) or only in the peripheral region (adults). Including IGF with FGF prevented an age-related decline in the beta/alpha-crystallin ratio but not in the gamma/beta-crystallin ratio. CONCLUSIONS: IGF-1 enhances the bFGF-induced fiber differentiation responses of lens epithelial cells in neonatal, weanling, and adult rats, partially restoring an age-related decline in the responsiveness of lens cells to FGF.