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Dynamic Change of Microglial States Across Onset of Degeneration and Müller Glia- Mediated Regeneration in a Zebrafish Model of Chronic Photoreceptor Degeneration Caused by pde6c Dysfunction
https://doi.org/10.15102/0002001101
https://doi.org/10.15102/0002001101e3fb20b3-d50a-44c0-ae78-031446385234
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RavishankarDarshiniExamAbstract.pdf (64 KB)
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RavishankarDarshiniSummary.pdf (94 KB)
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RavishankarDarshiniFulltext.pdf (9.2 MB)
Download is available from 2026/12/3.
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| Item type | デフォルトアイテムタイプ（フル）(1) | |||||||
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| PubDate | 2026-02-04 | |||||||
| Title | ||||||||
| Title | pde6c機能不全により慢性的な視細胞変性を起こすゼブラフィッシュモデルにおいて、視細胞変性の発症からミュラーグリアによる再生に至るまでにミクログリアが示すダイナミックな状態変化 | |||||||
| Language | ja | |||||||
| Title | ||||||||
| Title | Dynamic Change of Microglial States Across Onset of Degeneration and Müller Glia- Mediated Regeneration in a Zebrafish Model of Chronic Photoreceptor Degeneration Caused by pde6c Dysfunction | |||||||
| Language | en | |||||||
| Creator |
Ravishankar, Darshini
× Ravishankar, Darshini
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| Access Rights | ||||||||
| Access Rights | open access | |||||||
| Access Rights URI | http://purl.org/coar/access_right/c_abf2 | |||||||
| Rights | ||||||||
| Rights | © 2025 The Author. | |||||||
| Description | ||||||||
| Description Type | Abstract | |||||||
| Description | Microglia are immune sentinels of the central nervous system and contribute to the progression of acute retinal degeneration. However, the role of microglia at different stages of chronic degeneration is still unclear. Our lab has previously characterized zebrafish cyclic GMP-dependent phosphodiesterase 6c (pde6c) mutants, in which cones degenerate progressively over the lifespan of the fish. Rods are initially malformed but recover from 4 weeks post fertilization onwards through Müller glia-mediated regeneration. Taking advantage of this unique model, I investigate microglial responses to onset of degeneration and start of regeneration, as well as microglial heterogeneity, in the pde6c mutant retina. At onset of degeneration, microglia play a globally neuroprotective role by phagocytosing dying photoreceptors and upregulating neuroprotectionlinked genes, including p2ry12. I discover three distinct clusters of microglia, which all migrate towards the photoreceptors. Of these, the apoeb-enriched cluster 5d_Mg1 is the most reactive and expresses oxidative phosphorylation genes associated with repair. At start of regeneration, microglia hamper Müller glial proliferation in a time-dependent manner and express proinflammatory cytokine il1b. I discover two homeostasis-associated clusters and two diseaselinked clusters at this stage. One homeostatic cluster patrols the inner retina, while the other is a stem cell niche-associated, apoeb-enriched cluster. The two disease-linked clusters show pro- and anti-inflammatory characteristics respectively, are rare in the sibling, and associate principally with the photoreceptor outer segments in the mutant retina. This work provides the first characterization of microglial states in the homeostatic and chronically degenerating zebrafish retina, identifies candidate microglial states for future investigation, and emphasizes the critical role of timing on the impact of microglia on retinal degeneration. | |||||||
| Language | en | |||||||
| Resource Type | ||||||||
| Resource Type Identifier | http://purl.org/coar/resource_type/c_db06 | |||||||
| Resource Type | doctoral thesis | |||||||
| Version Type | ||||||||
| Version Type | VoR | |||||||
| Version Type Resource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||
| Identifier Registration | ||||||||
| Identifier Registration | 10.15102/0002001101 | |||||||
| Identifier Registration Type | JaLC | |||||||
| Dissertation Number | ||||||||
| Dissertation Number | 甲第218号 | |||||||
| Degree Name | ||||||||
| Language | en | |||||||
| Degree Name | Doctor of Philosophy | |||||||
| Date Granted | ||||||||
| Date Granted | 2025-11-30 | |||||||
| Degree Grantor | ||||||||
| Degree Grantor Name Identifier Scheme | kakenhi | |||||||
| Degree Grantor Name Identifier | 38005 | |||||||
| Language | en | |||||||
| Degree Grantor Name | Okinawa Institute of Science and Technology Graduate University | |||||||
