Faculty Sponsor: Dr. Julio Ramirez
Cell survival and axon regeneration are often limited in the central nervous system (CNS) following injury or disease, creating a significant need for novel therapeutic interventions that improve regeneration. The mouse optic nerve crush model mimics neurodegenerative diseases and traumatic CNS injuries by inducing progressive death of retinal ganglion cells (RGCs), the neurons whose axons were severed and do not regrow. Complement proteins of the innate immune system have been found to have neurotoxic, neuroprotective, and neurodegenerative roles in various injury and disease models, though their roles in cell survival and regeneration following optic nerve crush are largely unknown. Zinc plays a crucial role in a variety of cellular functions. Mobile zinc accumulates in amacrine cells and RGCs after optic nerve injury, and its removal by zinc chelation (TPEN or ZX1) increases RGC survival and axon regeneration after optic nerve injury. We tested the hypothesis that complement is required for these effects by assessing RGC survival and axon regeneration in C1q knock-out, C3 knock-out, C3 receptor CR3 knock-out, and wild-type control mice 14 days after optic nerve crush plus zinc chelation treatment (TPEN). Our data demonstrate that while neither C1q, C3, nor CR3 affect RGC survival, C1q, C3, and CR3 are all required for RGC axon regeneration. Further investigation into the role of the innate immune system in CNS axon regrowth may lead to the development of interventions to improve neuronal regeneration following injury.