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Diabetologia
Published in: Diabetologia 5/2015

Open Access 01-05-2015 | Article

Role of the receptor for advanced glycation endproducts (RAGE) in retinal vasodegenerative pathology during diabetes in mice

Authors: Carmel M. McVicar, Micheal Ward, Liza M. Colhoun, Jasenka Guduric-Fuchs, Angelika Bierhaus, Thomas Fleming, Andreas Schlotterer, Matthias Kolibabka, Hans-Peter Hammes, Mei Chen, Alan W. Stitt

Published in: Diabetologia | Issue 5/2015

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Abstract

Aims/hypothesis

The receptor for AGEs (RAGE) is linked to proinflammatory pathology in a range of tissues. The objective of this study was to assess the potential modulatory role of RAGE in diabetic retinopathy.

Methods

Diabetes was induced in wild-type (WT) and Rage −/− mice (also known as Ager −/− mice) using streptozotocin while non-diabetic control mice received saline. For all groups, blood glucose, HbA1c and retinal levels of methylglyoxal (MG) were evaluated up to 24 weeks post diabetes induction. After mice were killed, retinal glia and microglial activation, vasopermeability, leucostasis and degenerative microvasculature changes were determined.

Results

Retinal expression of RAGE in WT diabetic mice was increased after 12 weeks (p < 0.01) but not after 24 weeks. Rage −/− mice showed comparable diabetes but accumulated less MG and this corresponded to enhanced activity of the MG-detoxifying enzyme glyoxalase I in their retina when compared with WT mice. Diabetic Rage −/− mice showed significantly less vasopermeability, leucostasis and microglial activation (p < 0.05–0.001). Rage −/− mice were also protected against diabetes-related retinal acellular capillary formation (p < 0.001) but not against pericyte loss.

Conclusions/interpretation

Rage −/− in diabetic mice is protective against many retinopathic lesions, especially those related to innate immune responses. Inhibition of RAGE could be a therapeutic option to prevent diabetic retinopathy.
Appendix
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Metadata
Title
Role of the receptor for advanced glycation endproducts (RAGE) in retinal vasodegenerative pathology during diabetes in mice
Authors
Carmel M. McVicar
Micheal Ward
Liza M. Colhoun
Jasenka Guduric-Fuchs
Angelika Bierhaus
Thomas Fleming
Andreas Schlotterer
Matthias Kolibabka
Hans-Peter Hammes
Mei Chen
Alan W. Stitt
Publication date
01-05-2015
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 5/2015
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-015-3523-x

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