Epidermal growth factor and transforming growth factor alpha induce c-fos gene expression in retinal Muller cells in...

Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) are peptides that act at a common receptor and are mitogenic for immature astrocytes and trophic for developing brain neurons in vitro. However, a role for these growth factors in the mature nervous system has not been established. To investigate the actions of EGF and TGF alpha in the adult central nervous system (CNS) in vivo, the growth factors were injected into the vitreous cavity of adult male rabbits. After varying intervals, the retinas were examined for c-fos mRNA by Northern blot hybridization or Fos (and Fos-related antigen) protein by immunocytochemistry. EGF induction of c-fos mRNA occurs within 30 min and persists more than 4 hr. Fos nuclear immunostaining is induced selectively in nuclei of Muller cells by both EGF and TGF alpha. Fos-like immunoreactivity appears within 1 hr and persists more than 9 hr after EGF injection. These observations demonstrate that mature retinal Muller cells respond to exogenously applied EGF and TGF alpha in vivo, although the effect of the growth factors is not necessarily direct. The expression of c-fos and other immediate early genes provides a short-term marker that can be used to investigate the role of growth factors in normal retinal physiology and responses to injury.