Sirtuin 1 regulates lipid metabolism associated with optic nerve regeneration

Injury to the optic nerve may lead to axonal degeneration, followed by the gradual death of retinal ganglion cells (RGCs), which results in irreversible vision loss. In the present study the mechanism of optic nerve injury, and the following regeneration and repair processes associated with sirtuin 1 (SIRT1)‑regulated lipid metabolism were analyzed. In addition, the treatment of optic nerve injury using resveratrol was investigated. A rat model of optic nerve damage was prepared, and rats were divided into control, model and resveratrol groups. The model rats (with optic nerve damage) were treated with phosphate‑buffered saline or resveratrol once a day for seven, 14 and 21 days. The rats were then sacrificed and the optic nerve was dissected. The expression levels of SIRT1, sterol regulatory element‑binding protein 2 (SREBP‑2) and 3‑hydroxy‑3‑methylglutaryl‑CoA reductase (HMGCR) mRNA in the optic nerve were measured by reverse transcription‑quantitative polymerase chain reaction, and the protein expression of SIRT1, SREBP2 and HMGCR was evaluated by western blotting. In addition, the cholesterol level of the optic nerve was assessed. The retina was excised and the surviving RGCs were observed and counted. The morphology of the RGCs in the rat model of optic nerve injury changed; however, the degree of damage in rats treated with resveratrol was relatively small. The number of surviving RGCs and the cholesterol level in the RGCs from the model rats was observed to be restored by treatment with resveratrol following optic nerve damage. Additionally, the expression levels of SIRT1, SREBP‑2 and HMGCR mRNA and protein were restored by resveratrol treatment in the rats with optic nerve damage. Thus, resveratrol reversed certain features of the optic nerve injury damage via SIRT1 and SREBP‑2‑associated signaling pathways and the downstream regulated gene, HMGCR. Furthermore, resveratrol promoted cholesterol synthesis in, and repair of, RGCs. Therefore, SIRT1 may serve as a promising novel target for the treatment of optic nerve damage.