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Xiaoxi Qiao, Yue Li, Tongrong Zhou, Paul A Edwards, Hua Gao; Metformin improves retinal capillary perfusion in diabetic mice. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3591.
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© ARVO (1962-2015); The Authors (2016-present)
Blood flow change in diabetic retinopathy (DR) is widely recognized. Metformin treatment has been associated with improved hemodynamic responses in diabetes, but its role in retinal microcirculation remains unknown. This study examines the effect and possible mechanism of metformin on retinal blood flow in diabetic condition.
Diabetes was induced in C57BL/6 mice by intraperitoneal streptozotocin (STZ) injection. Metformin hydrochloride solution was administrated by gavage at 200 mg/kg/d after STZ injection for 10 weeks. Retinal blood flow was measured by fluorescein angiography (FA) video recordings after tail vein injection of 100 μl of 1% sodium fluorescein. The level of endothelin-1 (ET-1) in mouse serum as well as human retinal vascular endothelial cell (hRVEC) supernatant was measured using ELISA.
Among three groups including control, STZ-induced diabetic and metformin treated diabetic mice, no abnormalities were evident in fundus examination in any mice. FA recording analysis revealed a significant prolonged mean filling time of both central artery and microvascular beds in STZ-induced diabetic mice when compared with age-matched control mice (both p < 0.01). Metformin treatment for 10 weeks after diabetes induction completely blocked the extension of microvascular bed filling time (p < 0.001). The central arterial filling time appeared to have minimal effect by metformin. Although there was a slight extend filling time in the central vein of two diabetic groups, the difference did reach statistical significance when compared to control mice. Metformin also reduced ET-1 levels in serum of STZ mice as well as in supernatant of high glucose conditioned-hRVECs in vitro.
The impairment of retinal blood flow in STZ-induced diabetic mice occurs primarily in retinal artery and capillary. Early metformin treatment significantly improved retinal capillary perfusion, probably through down-regulation of the vasoconstrictive endothelin-1.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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