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Xiaoxi Qiao, Yue Li, Tongrong Zhou, Paul A Edwards, Hua Gao; Metformin preserves retinal function and reduces retinal leukostasis in diabetic mice. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6344.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic retinopathy (DR) is characterized by hyperglycemia-induced microvascular pathology and neuronal dysfunction in the retina of patients with type 2 diabetes. Metformin is recently found to be protective for vascular complications of diabetes by mechanisms beyond the glycemic control. This study was designed to investigate the effect of metformin on the retinal function and vasculature in a streptozotocin (STZ)-induced diabetic mouse model.
Diabetes was induced in young adult C57BL/6 mice by intraperitoneal injection of STZ in 5 consecutive days. Metformin hydrochloride oral solution was given to the mice by gavage at 200 mg/kg/d after STZ injection for 12 weeks. Scotopic electroretinography (ERG) was used to assess photoreceptor, Müller cell and bipolar cell function. The retinal vasculature was evaluated by fluorescent angiography (FA). The retinal leukostasis were quantified by immunofluorescent staining of adherent leukocytes in the retinal whole-mounts.
Substantial reduction in the amplitude of dark-adapted a-wave (p<0.05) and b-wave (p<0.001) was observed in the STZ-induced diabetic mice, compared with the normal control group. Metformin treatment for 12 weeks almost completely restored the a-wave amplitude (p=0.54 when compared with the normal control group), and effectively preserved the b-wave amplitude (p<0.01 when compared with the untreated diabetic group). No sign of microvascular angiopathy was noticed by FA in diabetic mice. Diabetic mouse showed a significant increased number of adherent leukocytes in the retinal vasculature (p<0.001 when compared with the normal control group). Metformin treatment markedly reduced the number of adherent leukocytes by 46% (p<0.001 when compared with the untreated diabetic group).
Metformin protects the retinal function and reduces diabetic leukostasis in STZ-induced diabetic mice. These findings are consistent with our preliminary observations in patients, and strongly suggest a beneficial effect of metformin on the visual function of DR patients, which merits further investigation.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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