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The DPP4 Inhibitor Linagliptin Protects from Experimental Diabetic Retinopathy

Nadine Dietrich1, Matthias Kolibabka1, Stephanie Busch1

  • 15th Medical Department, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany.

Plos One
|December 13, 2016
PubMed
Abstract

Insights

Linagliptin protects the diabetic retina by reducing microvascular damage and inflammation. This dipeptidyl peptidase 4 (DPP4) inhibitor preserves retinal cells and improves neuronal function in experimental models.

Area of Science:

  • Ophthalmology
  • Endocrinology
  • Diabetology

Background:

  • Dipeptidyl peptidase 4 (DPP4) inhibitors aid glycemic control in type 2 diabetes.
  • The impact of DPP4 inhibitors on the retinal neurovascular unit is not well understood.

Purpose of the Study:

  • To investigate the vasculo- and neuroprotective effects of linagliptin in experimental diabetic retinopathy.

Main Methods:

  • Assessed linagliptin's effects in STZ-diabetic Wistar rats and high glucose-cultivated C. elegans.
  • Measured retinal parameters including DPP4 activity, GLP-1, methylglyoxal, acellular capillaries, pericytes, and inflammatory markers.
  • Evaluated neuronal function in C. elegans using motility assays.

Main Results:

  • Linagliptin significantly reduced DPP4 activity and methylglyoxal, while increasing active GLP-1.
  • The drug diminished acellular capillaries, prevented pericyte and retinal ganglion cell loss, and reduced microglial activation.
  • Linagliptin decreased retinal IL-1beta expression and improved neuronal function in C. elegans.

Conclusions:

  • Linagliptin demonstrates protective effects on the diabetic retina's microvasculature.
  • These benefits are likely attributed to linagliptin's neuroprotective and antioxidative actions on the neurovascular unit.

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