Purpose:
The aim of this study was to evaluate the protective effects of melatonin on diabetic retinopathy(DR).
Methods:
Three groups of Sprague-Dawley (SD) rats were enrolled in this study:(1) a control group , (2) a diabetic group and (3) a diabetic group treated with melatonin(10mg/kg/day intraperitoneal). Diabetes was induced with a single dose of 60mg/kg i.p.streptozotocin (STZ). Rats were sacrificed separately at 4,8,12 weeks after diabetes induction. Retinas were extracted and were used for biochemical studies. Ten animals were included in each subgroup. Akt phosphorylation,heme oxygenase-1(HO-1),nuclear erythroid 2-related factor 2 (Nrf2), nuclear factor-kappa B (NF-ΚB) and inducible nitric oxide synthase (iNOS) mRNA and protein expressions were measured by Real-time PCR and Western Blot.
Results:
Nrf2 expression was significantly reduced 8 and 12 weeks after diabetes was induced compared with the control group (P<0.05) and melatonin upregulated its expression (P<0.05). The capacity of melatonin to modulate Nrf2 pathway was associated with increased HO-1 expression (P<0.05), which strengthens antioxidant defense. Further, melatonin also activated the reduced level of phosphorylated Akt and downregulated the elevated level of NF-ΚB and proinflammatory cytokine iNOS (P<0.05).
Conclusions:
Melatonin attenuated oxidative stress via the PI3K/Akt-Nrf2 signaling pathway and inflammation by decreasing NF-ΚB activation cascade, which might be responsible at least in part, for its protective effects in DR.
Keywords: melatonin • antioxidants • diabetic retinopathy