Stretch‐induced ATP release from optic nerve astrocytes

The mechanosensitive responses of neural systems have both protective and pathological roles, with the release of ATP and its dephosphorylation to adenosine central. The optic nerve is subjected to mechanical stresses upon elevation of intraocular pressure (IOP), and astrocytes play a key role. We thus asked whether optic nerve astrocytes released ATP upon stretch. Astrocytes cultured from neonatal rat optic nerves were grown on a silicone substrate and subjected to a 5% equilateral strain at 0.3 Hz for 2 min, with the luciferase assay used to determine extracellular levels of ATP. Stretching astrocytes led to a small but insignificant rise in ATP levels. However, stretching cells in the presence of ectoATPase inhibitors ARL67156 and βγmATP increased extracellular ATP levels 5 fold (p=0.03). EctoATPase inhibitors also increased ATP levels surrounding unstretched cells (p=0.03), suggesting active ectoATPases on astrocyte membranes normally reduced ATP released under both baseline and stimulated conditions. Preliminary data suggest the pannexin channel blocker carbenoxolone inhibited the release by 29% (p=0.04). In conclusion, optic nerve astrocytes release ATP when subjected to mild strain. However, high ectoATPase activity suggests that released ATP is rapidly degraded. It remains unclear whether extracellular ATP and adenosine affect retinal ganglion cell health in glaucomatous optic neuropathy. Grants: EY‐015537