Prior Exposure to Immunosuppressors Sensitizes Retinal Microglia and Accelerates Optic Nerve Regeneration in Zebrafish
As adult mammals lack the capacity to replace or repair damaged neurons, degeneration and trauma (and subsequent dysfunction) of the central nervous system (CNS) seriously constrains the patient’s life quality. Recent work has shown that appropriate modulation of acute neuroinflammation upon CNS inj...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2019/6135795 |
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| author | Ilse Bollaerts Jessie Van houcke An Beckers Kim Lemmens Sophie Vanhunsel Lies De Groef Lieve Moons |
| author_facet | Ilse Bollaerts Jessie Van houcke An Beckers Kim Lemmens Sophie Vanhunsel Lies De Groef Lieve Moons |
| author_sort | Ilse Bollaerts |
| collection | DOAJ |
| description | As adult mammals lack the capacity to replace or repair damaged neurons, degeneration and trauma (and subsequent dysfunction) of the central nervous system (CNS) seriously constrains the patient’s life quality. Recent work has shown that appropriate modulation of acute neuroinflammation upon CNS injury can trigger a regenerative response; yet, the underlying cellular and molecular mechanisms remain largely elusive. In contrast to mammals, zebrafish retain high regenerative capacities into adulthood and thus form a powerful model to study the contribution of neuroinflammation to successful regeneration. Here, we used pharmacological immunosuppression methods to study the role of microglia/macrophages during optic nerve regeneration in adult zebrafish. We first demonstrated that systemic immunosuppression with dexamethasone (dex) impedes regeneration after optic nerve injury. Secondly, and strikingly, local intravitreal application of dex or clodronate liposomes prior to injury was found to sensitize retinal microglia. Consequently, we observed an exaggerated inflammatory response to subsequent optic nerve damage, along with enhanced tectal reinnervation. In conclusion, we found a strong positive correlation between the acute inflammatory response in the retina and the regenerative capacity of the optic nerve in adult zebrafish subjected to nerve injury. |
| format | Article |
| id | doaj-art-b87d45222c144af681249af5c825c9ee |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-b87d45222c144af681249af5c825c9ee2025-02-03T01:23:24ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/61357956135795Prior Exposure to Immunosuppressors Sensitizes Retinal Microglia and Accelerates Optic Nerve Regeneration in ZebrafishIlse Bollaerts0Jessie Van houcke1An Beckers2Kim Lemmens3Sophie Vanhunsel4Lies De Groef5Lieve Moons6Neural Circuit Development and Regeneration Research Group, Department of Biology, KU Leuven, 3000 Leuven, BelgiumNeural Circuit Development and Regeneration Research Group, Department of Biology, KU Leuven, 3000 Leuven, BelgiumNeural Circuit Development and Regeneration Research Group, Department of Biology, KU Leuven, 3000 Leuven, BelgiumNeural Circuit Development and Regeneration Research Group, Department of Biology, KU Leuven, 3000 Leuven, BelgiumNeural Circuit Development and Regeneration Research Group, Department of Biology, KU Leuven, 3000 Leuven, BelgiumNeural Circuit Development and Regeneration Research Group, Department of Biology, KU Leuven, 3000 Leuven, BelgiumNeural Circuit Development and Regeneration Research Group, Department of Biology, KU Leuven, 3000 Leuven, BelgiumAs adult mammals lack the capacity to replace or repair damaged neurons, degeneration and trauma (and subsequent dysfunction) of the central nervous system (CNS) seriously constrains the patient’s life quality. Recent work has shown that appropriate modulation of acute neuroinflammation upon CNS injury can trigger a regenerative response; yet, the underlying cellular and molecular mechanisms remain largely elusive. In contrast to mammals, zebrafish retain high regenerative capacities into adulthood and thus form a powerful model to study the contribution of neuroinflammation to successful regeneration. Here, we used pharmacological immunosuppression methods to study the role of microglia/macrophages during optic nerve regeneration in adult zebrafish. We first demonstrated that systemic immunosuppression with dexamethasone (dex) impedes regeneration after optic nerve injury. Secondly, and strikingly, local intravitreal application of dex or clodronate liposomes prior to injury was found to sensitize retinal microglia. Consequently, we observed an exaggerated inflammatory response to subsequent optic nerve damage, along with enhanced tectal reinnervation. In conclusion, we found a strong positive correlation between the acute inflammatory response in the retina and the regenerative capacity of the optic nerve in adult zebrafish subjected to nerve injury.http://dx.doi.org/10.1155/2019/6135795 |
| spellingShingle | Ilse Bollaerts Jessie Van houcke An Beckers Kim Lemmens Sophie Vanhunsel Lies De Groef Lieve Moons Prior Exposure to Immunosuppressors Sensitizes Retinal Microglia and Accelerates Optic Nerve Regeneration in Zebrafish Mediators of Inflammation |
| title | Prior Exposure to Immunosuppressors Sensitizes Retinal Microglia and Accelerates Optic Nerve Regeneration in Zebrafish |
| title_full | Prior Exposure to Immunosuppressors Sensitizes Retinal Microglia and Accelerates Optic Nerve Regeneration in Zebrafish |
| title_fullStr | Prior Exposure to Immunosuppressors Sensitizes Retinal Microglia and Accelerates Optic Nerve Regeneration in Zebrafish |
| title_full_unstemmed | Prior Exposure to Immunosuppressors Sensitizes Retinal Microglia and Accelerates Optic Nerve Regeneration in Zebrafish |
| title_short | Prior Exposure to Immunosuppressors Sensitizes Retinal Microglia and Accelerates Optic Nerve Regeneration in Zebrafish |
| title_sort | prior exposure to immunosuppressors sensitizes retinal microglia and accelerates optic nerve regeneration in zebrafish |
| url | http://dx.doi.org/10.1155/2019/6135795 |
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