Activation of the non-canonical Wnt5a signaling pathway following optic nerve injury induces time-dependent changes in pro- and anti-inflammatory gene expression.

Optic nerve (ON) injury leads to retinal ganglion cell (RGC) degeneration and axonal atrophy. Wnt ligands are embryonic growth factors that regulate cellular differentiation and survival. We recently demonstrated that canonical and non-canonical Wnt signaling induces RGC survival and axonal regrowth after optic nerve crush (ONC) injury in mouse. Here, we investigated whether the non-canonical Wnt5a ligand induces pro-regenerative inflammation after ONC. Mice were intravitreally injected with Wnt5a or saline during ONC and retina tissue was collected for QPCR and immunofluorescence. We demonstrated that expression of arginase 1, a marker of anti-inflammatory microglia, was upregulated by Wnt5a in injured retinas, whereas iNOS, a marker of neurotoxic microglia, was suppressed. Wnt5a also induced time-dependent changes in pro-inflammatory genes Gal3, TNFα, P2RY12 and IL-6 and the anti-inflammatory gene IL-27. These results indicate that Wnt5a is an immunomodulatory ligand in the retina after ONC injury.