LINGO-1 Exerts neuroprotection in a rat glaucoma model

Abstract

Purpose: Axon regeneration in the central nervous system (CNS) is hindered by the presence of myelin inhibitory molecules. LINGO–1 is a new member of the myelin receptor complex besides NogoR1 and p75. This study was conducted to investigate the effect of LINGO–1 Fc fusion protein in the survival of retinal ganglion cells (RGCs) in a rat glaucoma model. Methods:Experimental glaucoma was induced in the right eye of each animal by elevating the intraocular pressure (IOP), and the left eye was used as control. Laser photocoagulation was applied twice to the episcleral and limbal veins at 7days interval. LINGO–1 Fc fusion protein was injected into the vitreous of the right eye after the first laser application. The loss of RGCs labeled by Fluoro–Gold was determined from flat–mounted retina 14 days later. Results:There was a significant loss of RGCs (13.2%) following the induction of elevated IOP in the PBS injection group. There was also a 10.6% RGCs loss in the human IgG injection group. A single intravitreal injection of LINGO–1 Fc fusion protein showed significant neuroprotective effect in enhancing the survival of RGCs (RGC death of –0.3%). Conclusions: These results provide evidence that LINGO–1 Fc fusion protein exerts neuroprotective activity to damaged RGCs in hypertensive eyes. It suggests that modulation of the interaction of myelin inhibitory proteins with their receptors has therapeutic application for CNS injury.