Abstract
Purpose:
Adenosine is a neuromodulator that is present in the retina. It has been suggested that adenosine may serve a neuroprotective role in the retina, based on electroretinogram (ERG) recordings from the rat retina. The purpose of this study was to assess the role of A2A and A3 adenosine receptors, known to be present in the rat retina, in generation and modulation of the rat ERG.
Methods:
Sprague Dawley rats were anesthetized by an intraperitoneal injection of S-ketamine (75mg/kg) and xylazine (6mg/kg). The flash ERG was recorded between an electrode placed on the cornea and a reference electrode on the lower canthus. Agonists and antagonists for A2A receptors, and for A3 receptors, and adenosine were each injected (5 µL) into the vitreous of six eyes with a NanoFil IOKit system (WPI, Inc, USA). Their effects on the components of the scotopic and photopic ERGs were examined, along with ERG flicker responses.
Results:
Adenosine [0.5 mM] caused an increase in the mean amplitude of the scotopic ERG a-wave from 68.0 + 7.7 µV to 96.7 + 13.7 µV (p=0.042). It also increased the mean amplitude of the scotopic b-wave from 236.5 + 38.4 µV to 305.3 + 41.6 µV (p=0.035). The A2A agonist CGS21680 [2mM] decreased the mean amplitude of both the ERG b-wave of dark adapted (298.2 + 21.5 µV to 212.5 + 19.3 µV; p=0.005) and light adapted eyes (124.3 + 17.7 µV to 87.8 + 11.2 µV; p=0.045). The mean scotopic oscillatory potentials (OPs) were decreased by CGS21680 (99.9 + 9.4 µV to 47.2 + 11.4 µV; p=0.023). ZM241385 [4mM], an A2A antagonist did not have any effect on any component of the ERG. The A3 agonist 2-CI-IB-MECA [0.5mM] increased the mean amplitude of the a-wave (91.4 + 15.4 µV to 152.9 + 21.2 µV; p=0.006), but decreased in the mean amplitude of the b-waves of both dark adapted (290.9 + 40.3 µV to 210 + 21.4 µV; p=0.022) and light adapted (170 + 19 µV to 135.9 + 11.4 µV; p=0.037) eyes. The scotopic OPs decreased in mean amplitude (79.6 + 15.2 µV to 39.2 + 3.9 µV; p=0.038) after 2-Cl-IB-MECA. The A3 antagonist VUF5574 increased the mean amplitude of both the a-wave (65.8 + 8.0 µV to 139.5 + 29.3 µV; p=0.046) and the b-wave of dark adapted eyes (223.7 + 20.3 µV to 312 µV + 38.7 µV; p=0.037). None of the ligands tested had any effect on the ERG flicker response.
Conclusions:
Retinal neurons that contain A2A and/or A3 adenosine receptors contribute to the generation of the ERG a- and b-waves and OPs.
Keywords: 410 adenosine •
510 electroretinography: non-clinical •
688 retina