CD200Fc Attenuates Retinal Glial Responses and RGCs Apoptosis After Optic Nerve Crush by Modulating CD200/CD200R1 Interaction

AbstractTo explore the hypothesis that CD200Fc, a CD200R1 agonist with anti-inflammatory properties, will inhibit retinal glial cells hyperactivation and retinal ganglion cells (RGCs) apoptosis after optic nerve injury. CD200Fc was immediately administered after optic nerve crush (ONC) once by intravitreal injection. Rats were euthanized at 5  days after ONC. The density of RGCs was counted by immunostaining of retina flat mounts for Brn3a. TUNEL assay, immunoblotting analysis of ionized calcium-binding adapter molecule 1(iba1) (microglia marker) and glial fibrillary acidic protein (GFAP) (astrocytes and Müller cells marker), RT-PCR an alysis of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin (IL)-8 and IL-10, ELISA measure protein levels of inflammatory cytokines and western blot analysis of CD200 and CD200R1 were evaluated. C D200Fc treatment suppressed ONC-induced RGCs loss through inhibition of RGCs apoptosis. Additionally, expression of glial cells activation markers GFAP and iba1 and production of pro-inflammatory cytokines (COX-2, iNOS, MCP-1, TNF-α, IL-8) were decreased in CD200Fc treated animals after ONC. Meanwh ile, anti-inflammatory cytokine IL-10 was increased by CD200Fc treatment in ONC-induced rat retina. Finally, we found that CD200Fc significantly inhibited ONC-induced increased in expression of CD200 and raised the already high basal CD200R1 expression...
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research