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RORγt Inhibitor-SR1001 Halts Retinal Inflammation, Capillary Degeneration, and the Progression of Diabetic Retinopathy.
Zapadka, Thomas E; Lindstrom, Sarah I; Taylor, Brooklyn E; Lee, Chieh A; Tang, Jie; Taylor, Zakary R R; Howell, Scott J; Taylor, Patricia R.
Afiliación
  • Zapadka TE; Department of Ophthalmology and Visual Sciences, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA.
  • Lindstrom SI; Louis Stokes Cleveland VA Medical Center, Cleveland, OH 44106, USA.
  • Taylor BE; Department of Ophthalmology and Visual Sciences, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA.
  • Lee CA; Department of Ophthalmology and Visual Sciences, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA.
  • Tang J; Department of Ophthalmology and Visual Sciences, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA.
  • Taylor ZRR; Department of Ophthalmology and Visual Sciences, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA.
  • Howell SJ; Department of Ophthalmology and Visual Sciences, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA.
  • Taylor PR; Department of Ophthalmology and Visual Sciences, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA.
Int J Mol Sci ; 21(10)2020 May 17.
Article en En | MEDLINE | ID: mdl-32429598
Diabetic retinopathy is a diabetes-mediated retinal microvascular disease that is the leading cause of blindness in the working-age population worldwide. Interleukin (IL)-17A is an inflammatory cytokine that has been previously shown to play a pivotal role in the promotion and progression of diabetic retinopathy. Retinoic acid-related orphan receptor gammaT (RORγt) is a ligand-dependent transcription factor that mediates IL-17A production. However, the role of RORγt in diabetes-mediated retinal inflammation and capillary degeneration, as well as its potential therapeutic attributes for diabetic retinopathy has not yet been determined. In the current study, we examined retinal inflammation and vascular pathology in streptozotocin-induced diabetic mice. We found RORγt expressing cells in the retinal vasculature of diabetic mice. Further, diabetes-mediated retinal inflammation, oxidative stress, and retinal endothelial cell death were all significantly lower in RORγt-/- mice. Finally, when a RORγt small molecule inhibitor (SR1001) was subcutaneously injected into diabetic mice, retinal inflammation and capillary degeneration were ameliorated. These findings establish a pathologic role for RORγt in the onset of diabetic retinopathy and identify a potentially novel therapeutic for this blinding disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vasos Retinianos / Sulfonamidas / Tiazoles / Capilares / Interleucina-17 / Diabetes Mellitus Experimental / Retinopatía Diabética / Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vasos Retinianos / Sulfonamidas / Tiazoles / Capilares / Interleucina-17 / Diabetes Mellitus Experimental / Retinopatía Diabética / Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza