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. Author manuscript; available in PMC: 2008 Aug 1.
Published in final edited form as: Invest Ophthalmol Vis Sci. 2007 Aug;48(8):3602–3609. doi: 10.1167/iovs.07-0131

FIGURE 3.

FIGURE 3

SRT501 attenuated RGC loss in a dose-dependent manner without reducing clinical EAE or inflammatory optic neuritis. (A) Control and EAE mice were treated with placebo or SRT501 on days 0, 3, 7, and 11 and were killed on day 14. Eyes from control mice treated with 100 μM SRT501 had no significant difference in RGC number from placebo-treated control eyes. EAE optic neuritis eyes had decreased RGC numbers (*P < 0.001) compared with controls. A small increase in RGC numbers in optic neuritis eyes treated with 6 μM SRT501 versus placebo was not significant. EAE optic neuritis eyes treated with 13 μM SRT501 had more RGCs than placebo (**P < 0.01). SRT501 (100 μM) further attenuated RGC loss, with RGC numbers increased compared with placebo (***P < 0.001) and with 6 μM SRT501–treated eyes (#P < 0.01) but no difference compared with control eyes. A trend toward increased RGC numbers in 100 μM SRT501 compared with 3 μM SRT501-treated eyes was not significant. (B) Mice immunized with PLP were evaluated daily for clinical EAE. No significant difference in EAE score was found between EAE mice treated with placebo or those treated with SRT501. (C) No significant difference in incidence of histologic optic neuritis was detected between EAE mice treated with placebo or SRT501. (D) The SIRT1 inhibitor sirtinol blocked the neuroprotective effects of SRT501. Sirtinol (100 μM) in control eyes did not significantly change RGC numbers compared with placebo-treated control eyes. EAE optic neuritis eyes had fewer RGCs than control eyes (*P < 0.001) and optic neuritis eyes treated with 100 μM SRT501 (**P < 0.001). Optic neuritis eyes treated with both 100 μM SRT501 and 100 μM sirtinol had fewer RGCs than optic neuritis eyes treated with 100 μM SRT501 alone (***P < 0.05), and RGC numbers were not significantly different from those of placebo-treated optic neuritis eyes.