Modulation of Cellular Survival Pathways and Components of the Adenosinergic System by Resveratrol in Chicken Embryo Retina

BACKGROUND Resveratrol (RV), an important polyphenol, has modulatory effects on cell survival pathways and components of the adenosinergic system in several study models, which may be related to its protective effects on CNS cells, although its effects are not yet clear in the retina. Therefore, we evaluated the effect of RV on survival pathways and the adenosine system in chick embryo retinas in physiological and pathological coditions. METHODS: 14-day-old White Leghorn eggs were injected with 10 and 20 mg/kg of RV diluted in DMSO, or only DMSO in the control group. After 48 hours, the retinas were dissected, and subjected or not to OGD for 50 minutes and then prepared for analysis by Western blot to evaluate the levels of CREB, AKT, ERK, Sirt1, A1 and A2A adenosine receptors, and ENT-1 adenosine transporter.  Data were analyzed using one-sample t-test or Two-way ANOVA in GraphPad Prism software, considering p<0.05 as significant. CEUA protocol number 2648161020. RESULTS: RV reduced p-CREB at 10 mg (p=0.0279) and 20 mg (p=0.0022); there was an increase in p-AKT at 10 mg (p=0.0034), with no effect at 20 mg (p=0.4512). A significant increase in p-ERK was also found at 10 mg (p=0.005) and a trend towards an increase at 20 mg (p=0.1135). In the adenosine system, RV 10 mg led to a reduction in A1 receptor (p=0.0023) and ENT-1 (p=0.1329), with the effect lost at 20 mg (A1: p=0.8194), (ENT-1: p=0.1792). There was a trend towards a decrease in A2A receptor at 10 mg (p=0.1) and 20 mg (n=2; p=not calculated) of RV. In turn, RV reduced SIRT1 levels at 20 mg (p=0.0281), but not at 10 mg (p=0.6452). In OGD, RV 10 mg was unable to inhibit the reduction in P-AKT (p>0.05), P-ERK (n=2; p=not calculated), and P-CREB (p<0.05). CONCLUSION: RV alters the activation of classical survival pathways and modulates the expression of components of the adenosinergic system.