Soluble Nogo66 receptor promotes retinal ganglion cell survival after optic nerve transection and ocular hypertension-induced glaucoma injuries

Three myelin proteins bind to the neuronal Nogo66 receptor (NgR1) that mediates the inhibition of axonal regeneration possibly via two transmembrane coreceptors, LINGO-1 and p75/TROY in the central nervous system (CNS). Modulation of the interactions of these myelin inhibitory proteins with NgR1 can overcome the inhibitory effects of CNS myelin in vitro and in vivo in models of spinal cord injuries. In addition to previous studies that have focused on the roles of NgR1 antagonists in promoting axonal regeneration, here we examined the effect of a soluble fragment of NgR1, sNgR1(27-310)-Fc fusion protein, when injected intravitrealy immediately after injury, on retinal ganglion cell (RGC) survival after ocular hypertension (chronic injury) and optic nerve transection (acute injury). The results showed that sNgR1(27-310)-Fc significantly reduced the loss of RGCs in the ocular hypertension glaucoma model 2 weeks after injury and promoted the survival of RGCs 7 days after optic nerve transection. Thus, sNgR1(27-310)-Fc may exhibit neuroprotective activity in addition to its NgR1 antagonist activity that promotes CNS axonal regeneration. Corresponding authors: KF So and DHS Lee. Supported by Biogen Idec Inc