title: Acute retinal ganglion cell injury caused by intraocular pressure spikes is mediated by endogenous extracellular ATP.
abstract: Elevated intraocular pressure may lead to retinal ganglion cell injury and consequent visual deficits. Chronic intraocular pressure increase is a major risk factor for glaucoma, a leading blinding disease, and permanent visual deficits can also occur following acute pressure increments due to trauma, acute glaucoma or refractive surgery. How pressure affects retinal neurons is not firmly established. Mechanical damage at the optic nerve head, reduced blood supply, inflammation and cytotoxic factors have all been called into play. Reasoning that the analysis of retinal neurons soon after pressure elevation would provide useful cues, we imaged individual ganglion cells in isolated rat retinas before and after short hydrostatic pressure increments. We found that slowly rising pressure to peaks observed in trauma, acute glaucoma or refractive surgery (50-90 mmHg) did not damage ganglion cells, whereas a rapid 1 min pulse to 50 mmHg injured 30% of these cells within 1 h. The severity of damage and the number of affected cells increased with stronger or repeated insults. Degrading extracellular ATP or blocking the P2X receptors for ATP prevented acute pressure-induced damage in ganglion cells. Similar effects were observed in vivo. A short intraocular pressure transient increased extracellular ATP levels in the eye fluids and damaged ganglion cells within 1 h. Reducing extracellular ATP in the eye prevented damage to ganglion cells and accelerated recovery of their response to light. These data show that rapid pressure transients induce acute ganglion cell injury and unveil the causal role of extracellular ATP elevation in such injury.
authors: Istituto di Neuroscienze CNR, Pisa, Italy.
authors: Valentina
authors: V
authors: Resta
authors: Elena
authors: E
authors: Novelli
authors: Giovanni
authors: G
authors: Vozzi
authors: Cristiano
authors: C
authors: Scarpa
authors: Matteo
authors: M
authors: Caleo
authors: Arti
authors: A
authors: Ahluwalia
authors: Anna
authors: A
authors: Solini
authors: Eleonora
authors: E
authors: Santini
authors: Vincenzo
authors: V
authors: Parisi
authors: Francesco
authors: F
authors: Di Virgilio
authors: Lucia
authors: L
authors: Galli-Resta
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D045604:Extracellular Fluid / Q000378:metabolism*; D005901:Glaucoma / Q000150:complications*; D007429:Intraocular Pressure / Q000502:physiology*; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D009898:Optic Disk / Q000503:physiopathology; D009924:Organ Culture Techniques; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D020318:Rats, Long-Evans; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058469:Receptors, Purinergic P2X; D012162:Retinal Degeneration / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D000255:Adenosine Triphosphate