The DPP4 inhibitor linagliptin protects from experimental diabetic retinopathy
Background/aims Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control in type 2 diabetes, however, their influence on the retinal neurovascular unit remains unclear. Methods Vasculo- and neuroprotective effects were assessed in experimental diabetic retinopathy and high glucose-cultivate...
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| Main Authors: | , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
December 12, 2016
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| In: |
PLOS ONE
Year: 2016, Volume: 11, Issue: 12 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0167853 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1371/journal.pone.0167853 Verlag, Volltext: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0167853 
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| Author Notes: | Nadine Dietrich, Matthias Kolibabka, Stephanie Busch, Petra Bugert, Ulrike Kaiser, Jihong Lin, Thomas Fleming, Michael Morcos, Thomas Klein, Andrea Schlotterer, Hans-Peter Hammes |
| Summary: | Background/aims Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control in type 2 diabetes, however, their influence on the retinal neurovascular unit remains unclear. Methods Vasculo- and neuroprotective effects were assessed in experimental diabetic retinopathy and high glucose-cultivated C. elegans, respectively. In STZ-diabetic Wistar rats (diabetes duration of 24 weeks), DPP4 activity (fluorometric assay), GLP-1 (ELISA), methylglyoxal (LC-MS/MS), acellular capillaries and pericytes (quantitative retinal morphometry), SDF-1a and heme oxygenase-1 (ELISA), HMGB-1, Iba1 and Thy1.1 (immunohistochemistry), nuclei in the ganglion cell layer, GFAP (western blot), and IL-1beta, Icam1, Cxcr4, catalase and beta-actin (quantitative RT-PCR) were determined. In C. elegans, neuronal function was determined using worm tracking software. Results Linagliptin decreased DPP4 activity by 77% and resulted in an 11.5-fold increase in active GLP-1. Blood glucose and HbA1c were reduced by 13% and 14% and retinal methylglyoxal by 66%. The increase in acellular capillaries was diminished by 70% and linagliptin prevented the loss of pericytes and retinal ganglion cells. The rise in Iba-1 positive microglia was reduced by 73% with linagliptin. In addition, the increase in retinal Il1b expression was decreased by 65%. As a functional correlate, impairment of motility (body bending frequency) was significantly prevented in C. elegans. Conclusion Our data suggest that linagliptin has a protective effect on the microvasculature of the diabetic retina, most likely due to a combination of neuroprotective and antioxidative effects of linagliptin on the neurovascular unit. |
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| Item Description: | Gesehen am 27.02.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0167853 |