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Diabetes induces IL-17A-Act1-FADD-dependent retinal endothelial cell death and capillary degeneration.
Lindstrom, Sarah I; Sigurdardottir, Sigrun; Zapadka, Thomas E; Tang, Jie; Liu, Haitao; Taylor, Brooklyn E; Smith, Dawn G; Lee, Chieh A; DeAngelis, John; Kern, Timothy S; Taylor, Patricia R.
Afiliación
  • Lindstrom SI; Department of Ophthalmology and Visual Sciences, Case Western Reserve University, School of Medicine, Cleveland, OH, United States of America.
  • Sigurdardottir S; Department of Ophthalmology and Visual Sciences, Case Western Reserve University, School of Medicine, Cleveland, OH, United States of America.
  • Zapadka TE; Department of Ophthalmology and Visual Sciences, Case Western Reserve University, School of Medicine, Cleveland, OH, United States of America.
  • Tang J; Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, OH, United States of America.
  • Liu H; Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, OH, United States of America.
  • Taylor BE; Department of Ophthalmology and Visual Sciences, Case Western Reserve University, School of Medicine, Cleveland, OH, United States of America.
  • Smith DG; Department of Ophthalmology and Visual Sciences, Case Western Reserve University, School of Medicine, Cleveland, OH, United States of America.
  • Lee CA; Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, OH, United States of America.
  • DeAngelis J; James E. Van Zandt VA Medical Center, Altoona, PA, United States of America.
  • Kern TS; Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, OH, United States of America; Louis Stokes VA Medical Center, Cleveland, OH, United States of America.
  • Taylor PR; Department of Ophthalmology and Visual Sciences, Case Western Reserve University, School of Medicine, Cleveland, OH, United States of America; Louis Stokes VA Medical Center, Cleveland, OH, United States of America. Electronic address: patricia.r.taylor@case.edu.
J Diabetes Complications ; 33(9): 668-674, 2019 09.
Article en En | MEDLINE | ID: mdl-31239234
PURPOSE: Diabetes leads to progressive complications such as diabetic retinopathy, which is the leading cause of blindness within the working-age population worldwide. Interleukin (IL)-17A is a cytokine that promotes and progresses diabetes. The objective of this study was to determine the role of IL-17A in retinal capillary degeneration, and to identify the mechanism that induces retinal endothelial cell death. These are clinically meaningful abnormalities that characterize early-stage non-proliferative diabetic retinopathy. METHODS: Retinal capillary degeneration was examined in vivo using the streptozotocin (STZ) diabetes murine model. Diabetic-hyperglycemia was sustained for an 8-month period in wild type (C57BL/6) and IL-17A-/- mice to elucidate the role of IL-17A in retinal capillary degeneration. Further, ex vivo studies were performed in retinal endothelial cells to identify the IL-17A-dependent mechanism that induces cell death. RESULTS: It was determined that diabetes-induced retinal capillary degeneration was significantly lower in IL-17A-/- mice. Further, retinal endothelial cell death occurred through an IL-17A/IL-17R ➔ Act1/FADD signaling cascade, which caused caspase-mediated apoptosis. CONCLUSION: These are the first findings that establish a pathologic role for IL-17A in retinal capillary degeneration. Further, a novel IL-17A-dependent apoptotic mechanism was discovered, which identifies potential therapeutic targets for the early onset of diabetic retinopathy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vasos Retinianos / Interleucina-17 / Proteínas Adaptadoras Transductoras de Señales / Diabetes Mellitus Experimental / Retinopatía Diabética / Proteína de Dominio de Muerte Asociada a Fas Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: J Diabetes Complications Asunto de la revista: ENDOCRINOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vasos Retinianos / Interleucina-17 / Proteínas Adaptadoras Transductoras de Señales / Diabetes Mellitus Experimental / Retinopatía Diabética / Proteína de Dominio de Muerte Asociada a Fas Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: J Diabetes Complications Asunto de la revista: ENDOCRINOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos