Soliño Manuel, Larrayoz Ignacio M, López Ester M, Vacotto Marina, Martignone Noelí, Rey-Funes Manuel, Martínez Alfredo, Girardi Elena, López-Costa Juan J
Universidad de Buenos Aires, Facultad de Medicina, Dpto. de Biología Celular, Histología, Embriología y Genética, Ciudad Autónoma de Buenos Aires, Argentina; CONICET-Universidad de Buenos Aires, Instituto de Biología Celular y Neurociencia "Prof. E. De Robertis¨ (IBCN), Ciudad Autónoma de Buenos Aires, Argentina.
Biomarkers and Molecular Signaling Group, Center for Biomedical Research of La Rioja (CIBIR), Logroño, Spain.
Neurosci Lett. 2018 Nov 20;687:259-267. doi: 10.1016/j.neulet.2018.09.053. Epub 2018 Oct 3.
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.
腺苷受体A1（A1R）和A2A（A2AR）的调节在不同的视网膜损伤模型中具有神经保护作用。为了了解视网膜变性的潜在机制，我们通过定量逆转录聚合酶链反应（qRT-PCR）、蛋白质免疫印迹法（WB）和免疫组织化学（IHC）研究了对照大鼠和持续光照（CI）大鼠视网膜中腺苷受体的表达情况。通过qRT-PCR观察到，在CI第1、5和7天，A1R、A2AR和A2BR mRNA显著增加（P < 0.0001）。此外，在CI第5天和第7天后检测到A3R mRNA显著增加。WB研究显示，CI第1天以及第5天和第7天A1R显著升高（P < 0.0001），而从CI第2天开始A2AR增加（P < 0.001）。CI第1天后，神经节细胞层、内核层以及外网状层和内网状层的A1R免疫反应性（A1R-IR）增加。CI第2天后，A1R-IR恢复到对照水平。CI第5天后，检测到A1R再次升高，并持续到CI第7天（P < 0.0001）。在CI第2天，神经节细胞层（GCL）和内核层（INL）的A2aR免疫反应性也显著升高，并在第5天和第7天下降（P < 0.0001）。CI第1天后观察到的A1R上调与氧化应激峰值相对应；而CI第2天A2aR的升高与光感受器的大量凋亡同时发生。我们推测，腺苷受体的早期调节可能会延迟或预防光感受器的退化。
