Neuroprotection of Retinal Ganglion Cells in Glaucoma by Blocking LINGO-1 Function or Using a Nogo-66 Receptor Antagonist

摘要: Abstract Glaucoma is a progressive neuropathy characterized by loss of vision as result the death retinal ganglion cells (RGCs). There are currently no effective neuroprotectants to treat this disorder. In series studies, we used LINGO-1 antagonists, Nogo-66 receptor (NgR1) sNgR-Fc, and brain-derived neurotrophic factor (BDNF) study neuroprotection RGCs in rat glaucoma model with chronic ocular hypertension. functional member NgR1/TROY P75 signaling complexes that prevent axonal regeneration activating RhoA central nervous system (CNS). NgR1 mediates inhibition presence three myelin proteins including Nogo-A, myelin-associated glycoprotein, oligodendrocyte glycoprotein CNS. was expressed increased after induction Blocking function soluble protein, LINGO-1-Fc, mAb 1A7 significantly promoted RGC survival 2 4 weeks hypertension also optic nerve transection. formed complex TrkB negatively regulated its activation retina injury. LINGO-1-Fc or upregulated phosphorylation high intraocular pressure BDNF antibody blocked on survival. Similarly, combination BDNF, provided more protection 4-week animals. Thus, antagonists protect regulating glaucoma. synaptic degeneration already detected early stage under elevated pressure, which preceded cell stage. The upregulation Nogo-A may be possible mechanism synapse Soluble (s) NgR-Fc at Furthermore, sNgR-Fc relieved 5 days, 4 weeks. This suggests there indeed an opportunity rescue undergoing alteration, but not yet committed die. These data suggest provide attractive therapeutic strategy synapses