The Nerve Growth Factor Administrated as Eye Drops Activates Mature and Precursor Cells in Subventricular Zone of Adult Rats

Abstract

The possibility to take advantage from the nerve growth factor (NGF) ability to induce recovery of damaged tissue has been largely explored in animal models and humans. Recently, the successful use of the ocular administration of NGF in ophthalmology, and the evidences that from the eyes NGF can access to the brain have stimulated new fields of research and open further perspectives to the clinical application of this neurotrophin. In our previous studies we have demonstrated the efficacy of NGF eye drop treatment to improved behavioural deficits and recover structural and biochemical alterations occurring follow brain lesion in animals. Since NGF exerts neuroreparative effects in brain by acting on mature neurons and neuronal precursors localised in germinal subventricular zone (SVZ), the present study has been aimed to evaluate the effects of NGF eye drop administration on the expression of the mitotic marker Ki67 in brain of adult rats. We found that a single ocular administration (10 μl) of 200 μg/mL NGF solution is sufficient to enhance the distribution of Ki67-positive cells also expressing p75 neurotrophin receptors in the proliferating layer of the SVZ. In addition, NGF treatment induces an increase of levels of brain-derived neurotrophic factor (BDNF) in forebrain. This data further supports the efficacy of ocular applied NGF to affect brain activities and suggests that NGF also by inducing local factors, including BDNF, can activate the machinery regulating the proliferation and maturation of neuronal precursor in brain.