Acute retinal ganglion cell injury caused by intraocular pressure spikes is mediated by endogenous extracellular ATP

Valentina Resta, Elena Novelli, Giovanni Vozzi, Cristiano Scarpa, Matteo Caleo, Arti Ahluwalia, Anna Solini, Eleonora Santini, Vincenzo Parisi, Francesco Di Virgilio, Lucia Galli-Resta

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2741-2754
Number of pages14
JournalEuropean Journal of Neuroscience
Volume25
Issue number9
DOIs
Publication statusPublished - May 2007

Keywords

  • Apyrase
  • Oxidized ATP
  • P2X receptors
  • Rat

ASJC Scopus subject areas

  • Neuroscience(all)

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    Resta, V., Novelli, E., Vozzi, G., Scarpa, C., Caleo, M., Ahluwalia, A., Solini, A., Santini, E., Parisi, V., Di Virgilio, F., & Galli-Resta, L. (2007). Acute retinal ganglion cell injury caused by intraocular pressure spikes is mediated by endogenous extracellular ATP. European Journal of Neuroscience, 25(9), 2741-2754. https://doi.org/10.1111/j.1460-9568.2007.05528.x