The expression of adenosine receptors changes throughout light induced retinal degeneration in the rat

Abstract

The modulation of adenosine receptors, A1 (A1R) and A2A (A2AR), is neuroprotective in different models of retinal injury. In order to understand the processes underlying retinal degeneration, we studied the expression of adenosine receptors in the retinas of control and continuously illuminated (CI) rats by qRT-PCR, Western blot (WB) and immunohistochemistry (IHC). Significant increases of A1R, A2AR, and A2BR mRNAs at 1, 5, and 7 days of CI (P < 0.0001) were observed by qRT-PCR. Also, a significant increase of A3R mRNA was detected after 5 and 7 days of CI. WB studies showed a significant rise of A1R on day 1 of CI and on days 5 and 7 (P < 0.0001), while A2AR increase was seen from 2 days of CI on (P < 0.001). After 1 day of CI, A1R immunoreactivity (A1R-IR) increased in ganglion cell layer, inner nuclear layer, and in both the outer and inner plexiform layers. After 2 days of CI, the A1R-IR went back to control levels. After 5 days of CI, a second rise in A1R, which persisted until 7 days of CI, was measured (P < 0.0001). A significant rise of A2aR immunoreactivity was also observed at day 2 of CI at GCL and INL and subsided at days 5 and 7 (P < 0.0001). The observed up-regulation of A1R after 1 day of CI, corresponds with the peak of oxidative stress; while the rise of A2aR at day 2 of CI, coincides with the massive apoptosis of photoreceptors. We postulate that an early modulation of adenosine receptors could delay or prevent the degeneration of photoreceptors.