Mangiferin Protects Retinal Ganglion Cells in Ischemic Mouse Retina via SIRT1

To investigate whether mangiferin can increase the viability of retinal ganglion cells (RGCs) in ischemic mouse retina, and to determine the possible mechanism of neuroprotection.

C57BL/6J mice underwent constant elevation of intraocular pressure for 60 min and received saline or mangiferin (30 mg/kg) intraperitoneally once daily until sacrifice. HIF-1α, GFAP and SIRT1 expression was assessed at 1, 4, and 7 days after retinal ischemia. Bax and Bcl-2 expression was also analyzed at 1 and 4 days. RGC survival was assessed by labeling flat-mounted retinas with Brn3a at 2 weeks after retinal ischemia. The effect of co-treatment with mangiferin and sirtinol (SIRT1 inhibitor) was also evaluated.

The expression of HIF-1α and GFAP was upregulated in saline-treated retinas within 7 days after ischemia. Mangiferin treatment suppressed this upregulation. The expression of SIRT1 was downregulated in saline-treated ischemic retinas. This downregulation was reversed by mangiferin treatment, resulting in a significant difference from saline-treated ischemic retinas. In mangiferin-treated ischemic retinas, Bax expression was downregulated, whereas Bcl-2 expression was upregulated in comparison with saline-treated ischemic retinas. Mangiferin treatment protected ischemic retinas against RGC loss. Treatment of sirtinol decreased the neuroprotective effect of mangiferin.

Our findings suggest that mangiferin has a neuroprotective effect on RGC through downregulation of HIF-1a and GFAP, and upregulation of SIRT1 in ischemic mouse retinas. We suggest that mangiferin might be a potential neuroprotective agent against RGC loss under oxidative stress.