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Yue Li, Tongrong Zhou, Andrew Hsu, Paul A Edwards, Xiaoxi Qiao; Metformin suppresses retinal microglia activation in diabetic mice. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3326.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal microglia are critically involved in neurodegeneration and neuroinflammation that precede microvascular impairment in diabetic retinopathy (DR). Our previous studies showed metformin treatment substantially suppressed inflammatory process in DR animal models and human patient vitreous. This study aims to evaluate the effect of metformin on retinal microglia activation in diabetic mice.
Streptozotocin (STZ)-induced diabetic C57BL/6 mice were given metformin hydrochloride solution (200 mg/kg/d) or normal saline by gavage for 12 weeks. Activation of retinal microglia was evaluated by immunofluorescent stain and western blot of ionized calcium binding adaptor molecule 1 (Iba1) in non-diabetic control, saline-treated, and metformin-treated diabetic mice.
There were significantly more Iba1-positive microglia in the retinal cross-sections of diabetic mice than those of non-diabetic control mice (p<0.05). Metformin treatment for 12 weeks moderately reduced the number of Iba1-positive retinal microglia when compared with saline treatment (p>0.05). The shape and intra-retinal distribution of Iba1-positive microglia were visibly different among the three groups. In the control group, the retinal microglia were spotted only within the ganglion cell layer and far less ramified than those in diabetic groups. In saline-treated diabetic mice, the distribution of the microglia processes expanded extensively in the inner and outer plexiform layers, and occasionally in the outer nuclear layer. Metformin treatment for 12 weeks prominently suppressed the filopodia-like ramification and outer plexiform layer distribution of the cell. Preliminary western blot data showed obviously enhanced Iba1 expression in the retina of diabetic mice, which was visibly reduced by metformin treatment.
Metformin suppressed retinal microglia activation in STZ-induced diabetic mice, which may be one of the underlying cellular mechanisms of the anti-inflammatory effect of metformin in DR. Further studies are underway in our lab to elucidate the effects of metformin in microglia associated neuroinflammation in DR.
This is a 2020 ARVO Annual Meeting abstract.
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