Purchase this article with an account.
Xiaoxi Qiao, Jing Han, Xiuli Liu, Tongrong Zhou, Paul A Edwards, Hua Gao; Metformin Protects Retinal Vascular Endothelial Cell Barrier Function from TNFα-induced Hyperpermeability in vitro and in vivo. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2302.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
We have previously reported that metformin, an anti-diabetic drug, has anti-angiogenic and anti-inflammatory effects directly on human retinal vascular endothelial cells (hRVECs). This study investigates if metformin also protects retinal vascular permeability from inflammatory insult induced by tumor necrosis factor-α (TNFα) in vitro and in vivo.
Primary hRVECs were grown in transwell to form monolayer and then challenged with TNFα with or without metformin treatment. Transwell permeability to FITC-dextran was assayed. The integrity of endothelial cell adhesion was determined by immunofluorescent staining of VE-cadherin and occludin. C57BL/6 mice with 50 ng intravitreal TNFα injection were treated with daily oral metformin or BSS vehicle 3 days before TNFα challenge for 10 days. Retinal vascular permeability was examined by quantifying albumin extravasation into the retinal parenchyma.
TNFα at 2.5 and 5.0 ng/ml induced a dose-dependent increase of hRVEC monolayer permeability to FITC-dextran. Metformin 5 mM pretreatment completely blocked 2.5 ng/ml TNFα effect and significantly attenuate 5.0 ng/ml TNFα effect (p < 0.05). Immunofluorescent staining of VE-cadherin and occludin revealed that metformin pretreatment dose-dependently prevented TNFα-induced disruptions of hRVEC monolayer integrity. In vivo study showed that TNFα intravitreal injection led to a 3-fold remarkable increase of retinal albumin level, indicating a severe breakdown of blood-retinal barrier. In contrast, metformin treated animals had a normal retinal albumin level in the BSS injected control group (n = 5, p < 0.05).
These in vitro and in vivo results demonstrate that metformin protects the integrity of the retinal vascular endothelial cell barrier function from TNFα-induced inflammatory insult. It indicates that metformin may provide additional benefit to control retinal vascular hyperpermeability in the conditions such as diabetic retinopathy and other inflammatory retinal diseases.
This PDF is available to Subscribers Only