June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Metformin Protects the Integrity and Function of Human Retinal Vascular Endothelial Cells from Diabetic Insults in vitro
Author Affiliations & Notes
  • Hua Gao
    Department of Ophthalmology, Henry Ford Health System, West Bloomfield, MI
  • Jing Han
    Department of Ophthalmology, Henry Ford Health System, West Bloomfield, MI
  • Xiuli Liu
    Department of Ophthalmology, Henry Ford Health System, West Bloomfield, MI
  • Tongrong Zhou
    Department of Ophthalmology, Henry Ford Health System, West Bloomfield, MI
  • Paul A Edwards
    Department of Ophthalmology, Henry Ford Health System, West Bloomfield, MI
  • Xiaoxi Qiao
    Department of Ophthalmology, Henry Ford Health System, West Bloomfield, MI
  • Footnotes
    Commercial Relationships Hua Gao, None; Jing Han, None; Xiuli Liu, None; Tongrong Zhou, None; Paul Edwards, None; Xiaoxi Qiao, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 2303. doi:
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      Hua Gao, Jing Han, Xiuli Liu, Tongrong Zhou, Paul A Edwards, Xiaoxi Qiao; Metformin Protects the Integrity and Function of Human Retinal Vascular Endothelial Cells from Diabetic Insults in vitro. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2303.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: In our previous clinic study, we have found that metformin use is associated with lower incidence of severe diabetic retinopathy. Subsequent in vitro study revealed that metformin has anti-angiogenic and anti-inflammatory effects on human retinal microvascular endothelial cells (hRVECs). This study investigates whether metformin protects hRVECs from direct high glucose or advanced glycation end products (AGEs) -induced insults.

Methods: Early passages of primary human RVECs (ACBRI 181) were exposed to either high glucose (30 mM) or AGEs (100 µg/ml) with or without metformin co-treatment. Transwell permeability of hRVECs monolayer to FITC-dextran was assayed. The production of monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) were determined by ELISA. The expression levels of occludin, claudin 5 and phosphorylated AMP-activated protein kinase (AMPK) were assessed by Western blot.

Results: AGEs induced a marked increase of hRVEC monolayer permeability to FITC-dextran by about 2 fold, which was completely blocked by 5 mM metformin at (p < 0.05). High glucose exposure led to a significant (p < 0.05) downregulation of adhesion molecules, claudin 5 and occludin by about 30%. Such effect was reversed partially by metformin at 2.5 mM and completely at 5 mM (p < 0.05). AGEs significantly increased secretion of inflammatory chemokines, MCP-1 and IL-8 in hRVECs by 2 fold and 1.7 fold, respectively (p < 0.001), and it decreased the level of phosphorylated AMPK in hRVEC. Metformin completely blocked AGEs-induced upsurge secretion of MCP-1 to below its baseline level, and IL-8 to basal level, respectively (p < 0.05). Meanwhile, metformin also restored phosphorylated AMPK (p < 0.05).

Conclusions: Metformin protects hRVECs from high glucose and/or AGEs-induced increase of permeability, reduction of adhesion molecules, and upregulation of inflammatory chemokines. These effects are at least partially mediated by restoring the activity of metabolic regulator AMPK. These results provide further support that metformin directly protect the integrity and normal function of retinal vascular endothelial cells from diabetic insults.

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