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Neutrophil elastase contributes to the pathological vascular permeability characteristic of diabetic retinopathy.
Liu, Haitao; Lessieur, Emma M; Saadane, Aicha; Lindstrom, Sarah I; Taylor, Patricia R; Kern, Timothy S.
Afiliación
  • Liu H; Department of Biology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
  • Lessieur EM; Department of Ophthalmology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People's Republic of China.
  • Saadane A; Center for Translational Vision Research, Department of Ophthalmology, Gavin Herbert Eye Institute, School of Medicine, University of California-Irvine, 829 Health Sciences Rd. Gillespie Neuroscience Research Facility, Room 2107, Irvine, CA, 92697, USA.
  • Lindstrom SI; Center for Translational Vision Research, Department of Ophthalmology, Gavin Herbert Eye Institute, School of Medicine, University of California-Irvine, 829 Health Sciences Rd. Gillespie Neuroscience Research Facility, Room 2107, Irvine, CA, 92697, USA.
  • Taylor PR; Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH, USA.
  • Kern TS; Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH, USA.
Diabetologia ; 62(12): 2365-2374, 2019 12.
Article en En | MEDLINE | ID: mdl-31612267
AIMS/HYPOTHESIS: Levels of neutrophil elastase, a serine protease secreted by neutrophils, are elevated in diabetes. The purpose of this study was to determine whether neutrophil elastase (NE) contributes to the diabetes-induced increase in retinal vascular permeability in mice with streptozotocin-induced diabetes, and, if so, to investigate the potential role of IL-17 in this process. METHODS: In vivo, diabetes was induced in neutrophil elastase-deficient (Elane-/-), Il-17a-/- and wild-type mice. After 8 months of diabetes, Elane-/- mice and wild-type age-matched control mice were injected with FITC-BSA. Fluorescence microscopy was used to assess leakage of FITC-BSA from the retinal vasculature into the neural retina. The level of NE in Il-17a-/- diabetic retina and sera were determined by ELISA. In vitro, the effect of NE on the permeability and viability of human retinal endothelial cells and the expression of junction proteins and adhesion molecules were studied. RESULTS: Eight months of diabetes resulted in increased retinal vascular permeability and levels of NE in retina and plasma of wild-type animals. All of these abnormalities were significantly inhibited in mice lacking the elastase. The diabetes-induced increase in NE was inhibited in mice lacking IL-17. In vitro, NE increased retinal endothelial cell permeability, which was partially inhibited by a myeloid differentiation primary response 88 (MyD88) inhibitor, NF-κB inhibitor, and protease-activated receptor (PAR)2 inhibitor. NE degraded vascular endothelial-cadherin (VE-cadherin) in a concentration-dependent manner. CONCLUSIONS/INTERPRETATION: IL-17 regulates NE expression in diabetes. NE contributes to vascular leakage in diabetic retinopathy, partially through activation of MyD88, NF-κB and PAR2 and degradation of VE-cadherin.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Retina / Vasos Retinianos / Barrera Hematorretinal / Elastasa de Leucocito / Retinopatía Diabética Límite: Animals Idioma: En Revista: Diabetologia Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Retina / Vasos Retinianos / Barrera Hematorretinal / Elastasa de Leucocito / Retinopatía Diabética Límite: Animals Idioma: En Revista: Diabetologia Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania