The retinal axon's pathfinding to the optic disk.

Abstract

Retinal ganglion cell (RGC) axons travel in radial routes unerringly toward the optic disk, their first intermediate target in the center of the eye. The path of the RGC growth cone is restricted to a narrow zone subjacent to the endfeet of Müller glial cells and the vitreal basal lamina. The present survey indicates that RGC growth cones are guided by many molecular cues along their pathway which are recognized by receptors on their surface. Growth-promoting molecules on Müller glial endfeet and in the basal lamina assist growth cones in maintaining contact with these elements. The repellant character of deeper retinal laminae discourages them from escaping the RGC axon layer. Cell adhesion/recognition proteins enable growth cones to fasciculate with preformed axons in their vicinity. It is still unclear whether the optic disk emits long range guidance components which enable the growth cones to steer toward it. Recent evidence in fish indicates the existence of an axonal receptor (neurolin) for a guidance component of unknown identity. Receptor blockade causes RGC axons to course in aberrant routes before they reach the disk. At the disk, axons receive signals to exit the retina. Contact with netrin-1 at the optic disk/nerve head encourages growth cones to turn into the nerve. This response requires the axonal netrin receptor DCC, laminin-1, beta-integrin and most likely the UNC5H netrin receptors which convert the growth encouraging signal into a repulsive one which drives growth cones into the nerve.