Glaucoma is an optic neuropathy and is currently one of the most common diseases leading to irreversible blindness. High intraocular pressure (IOP) progresses the pathogenesis of glaucoma, however glaucoma sometimes progresses despite IOP-lowering drugs or occurs even in patients with normal IOP, called normal tension glaucoma. Recently, the axonal degeneration that occurs before retinal ganglion cell (RGC) loss is thought to be involved in the pathogenesis of glaucoma. Meanwhile, the downregulation of intracellular cyclic adenosine monophosphate (cAMP) by axonal injury decreases the responsiveness of specific neurotrophic factors, thereby leading to RGC death. Interestingly, responsiveness to neurotrophic factors is restored when neurons are treated by pharmacological elevation of intracellular cAMP. G protein-coupled receptor 3 (GPR3) is abundantly expressed in various neurons and is unique in its ability to constitutively activate the Gs alpha subunit protein without ligands, thereby elevating intracellular cAMP levels. We have recently clarified that GPR3 is also expressed in RGCs and has neuroprotective effects against aging and retinal ischemia. Additionally, GPR3 transfection in RGCs using an adeno-associated virus vector augmented axonal regeneration after optic nerve crush. These findings support the potential importance of cAMP for axonal regeneration and the future application of GPR3 for neurodegenerative diseases, including glaucoma, using an adeno-associated virus vector.