Acidic Fibroblast Growth Factor Localization and Basic Fibroblast Growth Factor Binding Sites in the Eye and Optic Nerve

Senile dementia of the Alzheimer type is accompanied by visual impairment and damage of primary optic pathways. An alteration in the neurotrophic functions of some growth factors could be involved in the degeneration of retinal ganglion cells and their axons in the optic nerve. Among growth factors, acidic and basic fibroblast growth factors (aFGF, bFGF) are polypeptides which could be good candidates. They possess neurotrophic effects which have been demonstrated in vitro on a variety of cultured CNS neurons and in vivo by several lesion experiments. We are currently investigating whether FGF protein and exogenous labelled FGF binding sites are present in the retina and optic nerve to test this hypothesis. Preliminares results in the bovine model indicate that the aFGF protein is localized in the eye at the levels of ganglion cells, inner nuclear layer and receptors, whereas it is localized at the level of glial cells in the optic nerve. Binding sites of 125I-labelled bFGF are also present in the retina and optic nerve of bovine animals as well as human subjects. A low affinity bFGF binding site is colocalized with heparan sulfate proteoglycans of the retina basement membranes (inner limiting membrane, blood capillaries or vessels, Bruch’s membrane). A second specific site corresponding to cellular FGF receptors is also observed inside the retina on the pigmented epithelium and on three different layers colocalized with the inner and outer plexiform layers and with the inner segments of the photoreceptors. The presence of aFGF molecule and bFGF binding sites within these structures is a starting point for studying the possible implication of FGF in the survival of cells within the visual system during “normal” aging and in the etiology of Alzheimer’s disease.