Neutrophil-Derived Proteases Contribute to the Pathogenesis of Early Diabetic Retinopathy
| Autor: | Emma M. Lessieur, Timothy S. Kern, Jianying Kiser, Yunpeng Du, Aicha Saadane, Haitao Liu, Jie Tang |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Proteases Neutrophils Enzyme-Linked Immunosorbent Assay Inflammation Pharmacology Retina Diabetes Mellitus Experimental Pathogenesis Mice chemistry.chemical_compound medicine Animals Diabetic Retinopathy biology Superoxide business.industry Elane Sivelestat Endothelial Cells Leukostasis Retinal Flow Cytometry Mice Inbred C57BL Retinal Cell Biology chemistry Neutrophil elastase biology.protein medicine.symptom business neutrophil elastase microvasculature Peptide Hydrolases |
| Zdroj: | Investigative Ophthalmology & Visual Science |
| ISSN: | 1552-5783 |
| Popis: | Purpose Previous studies indicate that leukocytes, notably neutrophils, play a causal role in the capillary degeneration observed in diabetic retinopathy (DR), however, the mechanism by which they cause such degeneration is unknown. Neutrophil elastase (NE) is a protease released by neutrophils which participates in a variety of inflammatory diseases. In the present work, we investigated the potential involvement of NE in the development of early DR. Methods Experimental diabetes was induced in NE-deficient mice (Elane−/−), in mice treated daily with the NE inhibitor, sivelestat, and in mice overexpressing human alpha-1 antitrypsin (hAAT+). Mice were assessed for diabetes-induced retinal superoxide generation, inflammation, leukostasis, and capillary degeneration. Results In mice diabetic for 2 months, deletion of NE or selective inhibition of NE inhibited diabetes-induced retinal superoxide levels and inflammation, and inhibited leukocyte-mediated cytotoxicity of retinal endothelial cells. In mice diabetic for 8 months, genetic deletion of NE significantly inhibited diabetes-induced retinal capillary degeneration. Conclusions These results suggest that a protease released from neutrophils contributes to the development of DR, and that blocking NE activity could be a novel therapy to inhibit DR. |
| Databáze: | OpenAIRE |
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