Summary
This study identifies a perinuclear cAMP signaling compartment organized by mAKAPα that promotes retinal ganglion cell (RGC) survival and axon growth after optic nerve injury in mice. Enhancing cAMP signaling within this compartment by displacing a bound phosphodiesterase increased RGC survival in vivo, suggesting a potential therapeutic target for optic nerve and retinal diseases.
Key Findings
- Displacement of phosphodiesterase from the mAKAPα signalosome enhanced local cAMP signaling and increased retinal ganglion cell survival in vivo following optic nerve crush injury in mice of both sexes.
- mAKAPα-organized perinuclear cAMP compartment was shown to be necessary and sufficient for neurite outgrowth in vitro and RGC neuroprotection in vivo.
- Live-cell FRET imaging confirmed that manipulation of the mAKAPα compartment specifically altered local (perinuclear) rather than global cAMP levels.
Categories
Eye Health & Vision: Investigates retinal ganglion cell survival and axon regeneration following optic nerve crush injury, relevant to retinal neuroprotection.
Author(s)
T Boczek, EG Cameron, W Yu, X Xia
Publication Year
2019
Number of Citations
41
Related Publications
Eye Health & Vision
- Diminished pupillary light reflex at high irradiances in melanopsin-knockout mice
- Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa
- Melanopsin and rod–cone photoreceptors play different roles in mediating pupillary light responses during exposure to continuous light in humans
- Characteristic patterns of dendritic remodeling in early-stage glaucoma: evidence from genetically identified retinal ganglion cell types
- Intrinsically photosensitive melanopsin retinal ganglion cell contributions to the pupillary light reflex and circadian rhythm