Minocycline Inhibits Microglial Activation and Improves Visual Function in a Chronic Model of Age-Related Retinal Degeneration

Abstract

Age-related macular degeneration (AMD) is a chronic disease, which progresses slowly from early to late stages over many years. Inflammation critically contributes to the pathogenesis of AMD. Here, we investigated the therapeutic potential of minocycline in a chronic model of AMD (i.e., the LysMCre-Socs3fl/flCx3cr1gfp/gfp double knockout [DKO] mice). Five-month-old DKO and wild type (WT) (Socs3fl/fl) mice were gavage fed with minocycline (25 mg/kg daily) or vehicle (distilled water) for 3 months. At the end of the treatment, visual function and retinal changes were examined clinically (using electroretinography, fundus photograph and optic coherence tomography) and immunohistologically. Three months of minocycline treatment did not affect the body weight, behaviour and general health of WT and DKO mice. Minocycline treatment enhanced the a-/b-wave aptitudes and increased retinal thickness in both WT and DKO. DKO mouse retina expressed higher levels of Il1b, CD68 and CD86 and had mild microglial activation, and decreased numbers of arrestin+ photoreceptors, PKCα+ and secretagogin+ bipolar cells compared to WT mouse retina. Minocycline treatment reduced microglial activation and rescued retinal neuronal loss in DKO mice. Our results suggest that long-term minocycline treatment is safe and effective in controlling microglial activation and preserving visual function in chronic models of AMD.