| First Author | Lessieur EM | Year | 2021 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 62 |
| Issue | 13 | Pages | 7 |
| PubMed ID | 34643662 | Mgi Jnum | J:319538 |
| Mgi Id | MGI:6864025 | Doi | 10.1167/iovs.62.13.7 |
| Citation | Lessieur EM, et al. (2021) Neutrophil-Derived Proteases Contribute to the Pathogenesis of Early Diabetic Retinopathy. Invest Ophthalmol Vis Sci 62(13):7 |
| abstractText | 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. |
