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Investigation of the Effect of Combining Wnt Signaling and Inflammation Activators on Inflammatory Cells and Axonal Regrowth
Location: 6
Mentor: Dr. Abigail Hackam
Optic nerve (ON) injury leads to retinal ganglion cell (RGC) degeneration and axonal atrophy, processes both influenced by pro- and anti-inflammatory signals. We previously demonstrated that Wnt5a promotes axonal regeneration in mice after optic nerve crush (ONC) and regulates inflammatory cytokines, suggesting that Wnt5a-induced inflammation is pro-regenerative. We also found that Poly(I:C), a stronger inducer of inflammation, promotes axonal regeneration. However, when injected separately into the eye prior to ONC, saline, Wnt5a, and 1 µg Poly(I:C) yielded comparable levels of Iba1-positive inflammatory cells whereas Poly(I:C) and Wnt5a both promoted robust axonal regeneration. Here, we investigated whether combining Wnt5a with 1 µg Poly(I:C) injection 3 days after ONC promotes increased Iba1-positive inflammatory cells and axon regrowth. Since each treatment functions through different cellular pathways, we intended to determine if a combined approach would have a synergistic impact, especially when targeting the 3-day post ONC timeline with heightened prodegenerative M2-like microglia. Mice received Wnt5a injections prior to ONC, followed by Poly(I:C) or saline 3 days afterwards. After sectioning the retinas onto slides, immunohistochemistry was performed with an anti-Iba1 antibody, followed by imaging and quantification using Zen microscopy software. The combined Wnt5a and Poly(I:C) treatment resulted in increased Iba1+ cells compared with saline, Wnt5a, and Poly(I:C) alone, and Wnt5a and saline condition, which trended but has not reached significance. Ongoing experiments will provide additional evidence for increased inflammatory cells and demonstrate that a combined Wnt5a and Poly(I:C) treatment promotes increased axonal regrowth compared to the other conditions.
