Neutrophil-Derived Proteases Contribute to the Pathogenesis of Early Diabetic Retinopathy.
Invest Ophthalmol Vis Sci
; 62(13): 7, 2021 10 04.
Article
en En
| MEDLINE
| ID: mdl-34643662
ABSTRACT
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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Péptido Hidrolasas
/
Retina
/
Diabetes Mellitus Experimental
/
Retinopatía Diabética
/
Neutrófilos
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Invest Ophthalmol Vis Sci
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos