Insulin growth factor and epidermal growth factor trigger mitosis in lenses cultured in a serum-free medium

The mitogenicity of insulin, insulin growth factor (IGF), and epidermal growth factor (EGF) was evaluated on rabbit lenses cultured in medium KEI-4. IGF, the most highly purified of the insulin-like growth factors was a potent mitogen for mammalian lens epithelia cells. IGF and EGF triggered cell proliferation throughout the normally amitotic central and pre-equatorial region of the epithelium. The mitotic response elicited by IGF and EGF was dose dependent, was preceded by DNA synthesis, exceeded that engendered by equimolar insulin, and exhibited a chronology identical to that brought about by crystalline insulin. Lenses cultured in KEI-4 alone or in KEI-4 supplemented with growth hormone, proinsulin, the A and/or B chain of insulin, or MSA, another of the insulin-like growth factors belonging to the somatomedin family, did not show a mitotic response. Simultaneous exposure of the lens to IGF and EGF resulted in an increase in the total number of mitotic figures over that obtained with equimolar concentrations of IGF and EGF. Our results suggest that IGF or other insulin-like growth factors may be capable of regulating cell division in the mammalian lens in vivo. That the lens epithelium responded to IGF and EGF may indicate that lens epithelial cells are subject to multiple hormonal interaction. Since growth factors appear to be cell type specific, information obtained from the rabbit lens epithelium should be useful in delineating the factors and conditions required for the growth of cultured human lens cells.