LINGO-1 rescues retinal ganglion cells after optic nerve transection

Abstract

Transection of the optic nerve results in the death of retinal ganglion cells (RGCs). LINGO-1 is a nervous system-specific transmembrane protein that binds the Nogo-66 receptor/p75 signaling complex. We examined whether human LINGO-1-Fc (Sha Mi et. al. 2004 Nature Neuroscience) fusion protein enhances the survival of RGCs after optic nerve transection in adult rats. To label the RGCs, the animals received a piece of Fluoro-Gold soaked gelfoam at the nerve stump right after transecting the optic nerve 1.5 mm away from the optic disc, immediately followed by intravitreal injection of the treatment proteins. The number of surviving RGCs was determined from flat-mounted retina 7 days post-axotomy. There were 53% of total RGCs survived after the transection. LINGO-1-Fc fusion protein treatment enhanced the survival of RGCs to 83%. Treatment with the same amount of control protein did not increase RGC survival. The survival effects of the treatments were similar at 7 days post-axotomy if RGCs were prelabeled by placing a piece of Fluoro-Gold soaked gelfoam on the superior colliculus 1 week before transecting the optic nerve. It has been demonstrated that LINGO-1 is required for the inhibitory effects of myelin on axonal regeneration in the injured CNS (Sha Mi et. al. 2004 Nature Neuroscience). Although the mechanism of LINGO-1-Fc on promoting neuronal survival requires further elucidation, LINGO-1-Fc fusion protein is a potential candidate for the therapeutic treatment of optic nerve injury.