Ectopic expression of melanopsin promotes axonal regeneration in retinal ganglion cells via cAMP and TRPC signaling.

Viral expression of melanopsin (OPN4) in retinal ganglion cells promotes optic-nerve-crush axonal regeneration, with TRPC- and cAMP-dependent light-response components linked to regrowth.

• Why it matters: Mammalian RGCs regenerate only minimally after axotomy, and progress is limited by potential cell-type-specific barriers that remain poorly overcome.
• What they did: The authors virally expressed OPN4 broadly in RGCs, correlated infected +OPN4 RGC light responses with regeneration after optic-nerve crush, and used TRPC6/7 or AC2/4/7 genetic ablation plus cell-permeant cAMP rescue.
• The result: Disrupting TRPC channels or AC2/4/7 largely attenuated regeneration in +OPN4 αRGCs, while cAMP rescued the AC2/4/7 phenotype and potentiated regeneration in some +OPN4 non-αRGCs.