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PDGF Receptor Alpha Signaling Is Key for Müller Cell Homeostasis Functions.
Díaz-Lezama, Nundehui; Wolf, Anne; Koch, Susanne; Pfaller, Anna M; Biber, Josef; Guillonneau, Xavier; Langmann, Thomas; Grosche, Antje.
Afiliación
  • Díaz-Lezama N; Department of Physiological Genomics, Biomedical Center, Ludwig-Maximilians-Universität München, D-82152 Planegg-Martinsried, Germany.
  • Wolf A; Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50931 Cologne, Germany.
  • Koch S; Department of Physiological Genomics, Biomedical Center, Ludwig-Maximilians-Universität München, D-82152 Planegg-Martinsried, Germany.
  • Pfaller AM; Department of Physiological Genomics, Biomedical Center, Ludwig-Maximilians-Universität München, D-82152 Planegg-Martinsried, Germany.
  • Biber J; Department of Physiological Genomics, Biomedical Center, Ludwig-Maximilians-Universität München, D-82152 Planegg-Martinsried, Germany.
  • Guillonneau X; Institut de la Vision, INSERM, CNRS, Sorbonne Université, F-75012 Paris, France.
  • Langmann T; Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50931 Cologne, Germany.
  • Grosche A; Department of Physiological Genomics, Biomedical Center, Ludwig-Maximilians-Universität München, D-82152 Planegg-Martinsried, Germany.
Int J Mol Sci ; 22(3)2021 Jan 25.
Article en En | MEDLINE | ID: mdl-33503976
Müller cells, the major retinal macroglia, are key to maintaining vascular integrity as well as retinal fluid and ion homeostasis. Although platelet derived growth factor (PDGF) receptor expression in Müller glia has been reported earlier, their actual role for Müller cell function and intimate interaction with cells of the retinal neurovascular unit remains unclear. To close this gap of knowledge, Müller cell-specific PDGF receptor alpha (PDGFRα) knockout (KO) mice were generated, characterized, and subjected to a model of choroidal neovascularization (CNV). PDGFRα-deficient Müller cells could not counterbalance hypoosmotic stress as efficiently as their wildtype counterparts. In wildtypes, the PDGFRα ligand PDGF-BB prevented Müller cell swelling induced by the administration of barium ions. This effect could be blocked by the PDGFR family inhibitor AC710. PDGF-BB could not restore the capability of an efficient volume regulation in PDGFRα KO Müller cells. Additionally, PDGFRα KO mice displayed reduced rod and cone-driven light responses. Altogether, these findings suggest that Müller glial PDGFRα is central for retinal functions under physiological conditions. In contrast, Müller cell-specific PDGFRα KO resulted in less vascular leakage and smaller lesion areas in the CNV model. Of note, the effect size was comparable to pharmacological blockade of PDGF signaling alone or in combination with anti-vascular endothelial growth factor (VEGF) therapy-a treatment regimen currently being tested in clinical trials. These data imply that targeting PDGF to treat retinal neovascular diseases may have short-term beneficial effects, but may elicit unwarranted side effects given the putative negative effects on Müller cell homeostatic functions potentially interfering with a long-term positive outcome.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Receptor alfa de Factor de Crecimiento Derivado de Plaquetas / Células Ependimogliales / Homeostasis Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Receptor alfa de Factor de Crecimiento Derivado de Plaquetas / Células Ependimogliales / Homeostasis Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza