Monoclonal antibodies to nerve growth factor affect the postnatal development of the visual system.

Abstract

Exogenous supply of nerve growth factor (NGF) prevents the effects of monocular deprivation. This suggests that visual afferents may be competing for an endogenous neurotrophic factor, related to NGF, whose production by postsynaptic cells depends on the activity of afferent fibers. To test the hypothesis that endogenous NGF may play a role in the functional and anatomical development of the rat geniculo cortical system, the physiological action of NGF in the rat visual system was antagonized by using two independent monoclonal antibodies which neutralize NGF (alpha D11 and 4C8). To provide a continuous supply of antibodies during the period of visual cortical plasticity, alpha D11 or 4C8 antibody-producing hybridoma cells were implanted in the lateral ventricle of rats at postnatal day 15. This resulted in dramatic alterations of two of the most important parameters characterizing the functional development of the visual system, namely, visual acuity and binocularity of cortical neurons and in shrinkage of cells in the lateral geniculate nucleus. This demonstrates that the action of endogenous NGF is necessary for the normal functional and anatomical development of the geniculocortical system.