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CD74 indicates microglial activation in experimental diabetic retinopathy and exogenous methylglyoxal mimics the response in normoglycemic retina

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Abstract

Diabetes induces vasoregression, neurodegeneration and glial activation in the retina. Formation of advanced glycation endoproducts (AGEs) is increased in diabetes and contributes to the pathogenesis of diabetic retinopathy. CD74 is increased in activated microglia in a rat model developing both neurodegeneration and vasoregression. In this study, we aimed at investigating whether glucose and major AGE precursor methylglyoxal induce increased CD74 expression in the retina. Expression of CD74 in retinal microglia was analyzed in streptozotocin-diabetic rats by wholemount immunofluorescence. Nondiabetic mice were intravitreally injected with methylglyoxal. Expression of CD74 was studied by retinal wholemount immunofluorescence and quantitative real-time PCR, 48 h after the injection. CD74-positive cells were increased in diabetic 4-month retinas. These cells represented a subpopulation of CD11b-labeled activated microglia and were mainly located in the superficial vascular layer (13.7-fold increase compared to nondiabetic group). Methylglyoxal induced an 9.4-fold increase of CD74-positive cells in the superficial vascular layer and elevated gene expression of CD74 in the mouse retina 2.8-fold. In summary, we identified CD74 as a microglial activation marker in the diabetic retina. Exogenous methylglyoxal mimics the response in normoglycemic retina. This suggests that methylglyoxal is important in mediating microglial activation in the diabetic retina.

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Acknowledgments

This study was supported by grants from the DFG (Deutsche Forschungsgemeinschaft), the DDG (Deutsche Diabetes Gesellschaft) and the EFSD (European Foundation for the Study of Diabetes). The authors thank P. Bugert and U. Kaiser for their excellent technical assistance.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

Human and animal rights

All applicable national and institutional guidelines for the care and use of animals were followed.

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This article does not contain any studies with human participants performed by any of the authors.

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Authors and Affiliations

  1. 5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany

    Jing Wang, Jihong Lin, Andreas Schlotterer, Liang Wu, Stephanie Busch, Nadine Dietrich & Hans-Peter Hammes

  2. Department of Medicine I and Clinical Chemistry, University Hospital Heidelberg, Heidelberg, Germany

    Thomas Fleming

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  1. Jing Wang
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  2. Jihong Lin
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  3. Andreas Schlotterer
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  4. Liang Wu
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  5. Thomas Fleming
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  6. Stephanie Busch
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  7. Nadine Dietrich
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  8. Hans-Peter Hammes
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Correspondence to Hans-Peter Hammes.

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Wang, J., Lin, J., Schlotterer, A. et al. CD74 indicates microglial activation in experimental diabetic retinopathy and exogenous methylglyoxal mimics the response in normoglycemic retina. Acta Diabetol 51, 813–821 (2014). https://doi.org/10.1007/s00592-014-0616-9

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  • DOI: https://doi.org/10.1007/s00592-014-0616-9

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