Characterization of Developmentally Downregulated Nfe2l3 in Retinal Ganglion Cell Survival and Axon Regeneration

Retinal ganglion cells (RGCs) are central nervous system projection neurons essential for transmitting visual information from the eye to the brain. Damage to RGCs, caused by conditions such as glaucoma and traumatic optic neuropathy (TON), may lead to vision loss or blindness, as adult RGCs lack regenerative capacity. This study focuses on Nfe2l3 (Nrf3), a developmentally downregulated transcription factor known to mediate cellular responses to oxidative stress, a key pathological event following optic nerve injury. We hypothesized that overexpressing Nfe2l3 in RGCs would enhance their survival and promote axon regeneration after optic nerve crush (ONC) injury. To test this, we utilized an AAV2 vector to overexpress Nfe2l3 in RGCs and assessed its effects on RGC survival and axon regeneration in vivo. Results showed a significant increase in RGC survival (approximately 20% compared to controls) and robust axon regeneration, with fibers extending around 3 mm beyond the injury site. These findings indicate Nfe2l3’s potential as a therapeutic target for optic nerve repair and treatment of vision loss due to RGC damage.