Nerve growth factor: a mitogenic signal for retinal Müller glial cells

Knowledge of the effects of nerve growth factor (NGF) on glia is limited. A CNS site where NGF-glial interactions may occur is the retina. NGF is endogenous to the retina, and the retinal Müller glial cells have NGF receptors. Here, we examined the possibility that NGF may be a mitogen for Müller glial cells, which often proliferate in response to pathophysiological conditions. Experiments were performed on cultured glial cells from the adult human retina. Exposure of cultured Müller glial cells to 2.5 S NGF under serum-free conditions resulted in a concentration-dependent increase in cell number and bromodeoxyuridine incorporation into nuclei. The half-maximally effective concentration was 0.04 ng/ml (1.5 pM), consistent with activation of high affinity NGF receptors. K252a, a blocker of the neurotrophin family of tyrosine kinase-linked receptors, potently inhibited the proliferative effect of NGF. Transforming growth factor beta-2, another growth factor endogenous to the retina, inhibited the mitogenic response to NGF. These findings indicate that human Müller glial cells in culture express functional NGF receptors and that the response of Müller cells to NGF can be modulated by other growth factors.