Abstract: Objective To investigate the protective effect of melatonin (MEL) on retinal oxidative damage in agerelated macular degeneration (AMD) model mice and its effect on silent mating type information regulation 2 homolog 1 (SIRT1)/forkhead box transcription factor O1 (FOXO1) pathway. Methods Ninety mice were divided into normal group, model group, MEL low-dose, medium-dose and high-dose groups by random number table method, with 18 mice in each group. Except for the normal group, mice in the other groups were injected with 25 µL/g NaIO3 through tail vein to prepare AMD mouse model. Mice in the low-dose, medium-dose and high-dose MEL groups were gavaged with 10, 20 and 40 mg/kg MEL, respectively. Mice in the normal group and model group were gavaged with the same volume of normal saline, once a day, for a consecutive week. Fundus fluorescein angiography (FFA) was performed by fundus fluorescein angiography, and retinal thickness was detected by optical coherence tomography (OCT). The morphology of retina was detected by HE staining. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) in serum of orbital venous blood were detected by kit. The protein levels of SIRT1, FOXO1 and Ac-FOXO1 were detected by Western blot assay. Results In the model group, the optic disc disappeared, the blood vessels contracted, the retina became white, the blood vessels ruptured, the cells in each layer of retina arranged disorderly, the cells in the outer nuclear layer arranged loosely, the cells embedded in the inner/outer segment, and the cells in the inner nuclear layer enlarged and arranged loosely. With the increase of MEL dose, the above symptoms were gradually improved. Compared with the normal group, the retinal thickness, orbital venous blood SOD, GSH-Px, CAT activity, and the protein levels of SIRT1 and Ac-FOXO1/FOXO1 in the retina decreased in the model group (P＜0.05). Compared with the model group, the retinal thickness, the activities of SOD, GSH-Px, CAT and the level of SIRT1 protein increased in the three MEL dose groups. The protein levels of ACFoxO1/FoxO1 in retina increased in MEL medium and high dose groups (P＜0.05). Conclusion MEL may protect the retina oxidative damage of AMD model mice by activating SIRT1/FOXO1 pathway.

Key words: melatonin, macular degeneration, age factors, oxidative stress, retinal oxidative damage, SIRT1/FOXO1 pathway