PDGF Receptor Alpha Signaling Is Key for Müller Cell Homeostasis Functions
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 inte...
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| Format: | Article |
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MDPI AG
2021-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/3/1174 |
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| author | Nundehui Díaz-Lezama Anne Wolf Susanne Koch Anna M. Pfaller Josef Biber Xavier Guillonneau Thomas Langmann Antje Grosche |
| author_facet | Nundehui Díaz-Lezama Anne Wolf Susanne Koch Anna M. Pfaller Josef Biber Xavier Guillonneau Thomas Langmann Antje Grosche |
| author_sort | Nundehui Díaz-Lezama |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T03:43:19Z |
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| id | doaj.art-4743edba5fee4f6ea3dc75736a78cdc9 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T03:43:19Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4743edba5fee4f6ea3dc75736a78cdc92023-12-03T14:36:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-01223117410.3390/ijms22031174PDGF Receptor Alpha Signaling Is Key for Müller Cell Homeostasis FunctionsNundehui Díaz-Lezama0Anne Wolf1Susanne Koch2Anna M. Pfaller3Josef Biber4Xavier Guillonneau5Thomas Langmann6Antje Grosche7Department of Physiological Genomics, Biomedical Center, Ludwig-Maximilians-Universität München, D-82152 Planegg-Martinsried, GermanyLaboratory for Experimental Immunology of the Eye, Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50931 Cologne, GermanyDepartment of Physiological Genomics, Biomedical Center, Ludwig-Maximilians-Universität München, D-82152 Planegg-Martinsried, GermanyDepartment of Physiological Genomics, Biomedical Center, Ludwig-Maximilians-Universität München, D-82152 Planegg-Martinsried, GermanyDepartment of Physiological Genomics, Biomedical Center, Ludwig-Maximilians-Universität München, D-82152 Planegg-Martinsried, GermanyInstitut de la Vision, INSERM, CNRS, Sorbonne Université, F-75012 Paris, FranceLaboratory for Experimental Immunology of the Eye, Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50931 Cologne, GermanyDepartment of Physiological Genomics, Biomedical Center, Ludwig-Maximilians-Universität München, D-82152 Planegg-Martinsried, GermanyMüller 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.https://www.mdpi.com/1422-0067/22/3/1174Müller cellsretinaPDGF receptor alphachoroidal neovascularizationgliosis |
| spellingShingle | Nundehui Díaz-Lezama Anne Wolf Susanne Koch Anna M. Pfaller Josef Biber Xavier Guillonneau Thomas Langmann Antje Grosche PDGF Receptor Alpha Signaling Is Key for Müller Cell Homeostasis Functions International Journal of Molecular Sciences Müller cells retina PDGF receptor alpha choroidal neovascularization gliosis |
| title | PDGF Receptor Alpha Signaling Is Key for Müller Cell Homeostasis Functions |
| title_full | PDGF Receptor Alpha Signaling Is Key for Müller Cell Homeostasis Functions |
| title_fullStr | PDGF Receptor Alpha Signaling Is Key for Müller Cell Homeostasis Functions |
| title_full_unstemmed | PDGF Receptor Alpha Signaling Is Key for Müller Cell Homeostasis Functions |
| title_short | PDGF Receptor Alpha Signaling Is Key for Müller Cell Homeostasis Functions |
| title_sort | pdgf receptor alpha signaling is key for muller cell homeostasis functions |
| topic | Müller cells retina PDGF receptor alpha choroidal neovascularization gliosis |
| url | https://www.mdpi.com/1422-0067/22/3/1174 |
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