A Dynamic Change of Microglial States Occurs During the Transition From Photoreceptor Degeneration to Regeneration in Zebrafish pde6c Mutants.

Overview

Authors: Darshini Ravishankar¹, Yuki Takeuchi¹, Ichiro Masai¹

ORCID iDs: Darshini Ravishankar, Yuki Takeuchi, Ichiro Masai

Developmental Neurobiology Unit Okinawa Institute of Science and Technology Graduate University Okinawa Japan

Institutions: Okinawa Institute of Science and Technology Graduate University (Japan)

Journal: Glia, volume 74, issue 6, article e70158

Dates: received 30 July 2025; accepted 31 March 2026; published online 17 April 2026; in print June 2026

Type: Research article · Language: English

License: CC BY-NC

Identifiers: DOI 10.1002/glia.70158 · PMID 41995141 · PMCID PMC13088749 · OpenAlex W7154750607

Open access: hybrid, a free copy (OpenAlex)

Status: data only

Categories: genetics / omics (modality), zebrafish (organism), cellular / molecular (subfield)

Methods: Smoothing, state filtering, decompositions, Evoked potentials

Keywords: microglia, neuronal regeneration, pde6c, photoreceptor degeneration, zebrafish

MeSH: Cyclic Nucleotide Phosphodiesterases, Type 6*, Microglia*, Nerve Regeneration*, Retinal Degeneration*, Zebrafish Proteins*, Animals, Animals, Genetically Modified, Mutation, Retina, Zebrafish (* major topic)

Topic: Neuroinflammation and Neurodegeneration Mechanisms (Neurology, Neuroscience), according to OpenAlex

Funding: Okinawa Institute of Science and Technology Graduate University; Japan Society for the Promotion of Science (22KJ3081, 22J10161)

Citations: cited by 2 papers (Europe PMC); 81 references in the paper

Abstract

Microglia, brain‐resident immune cells, maintain brain homeostasis. However, homeostatic microglia dynamically change into disease‐associated microglia in human neurodegenerative diseases. Furthermore, microglia‐mediated inflammation is required to initiate neuronal regeneration in zebrafish brain. To understand how functional states of microglia are regulated in response to neuronal degeneration and regeneration, we focused on pde6c mutants, a chronic photoreceptor degeneration zebrafish model. We conducted scRNA‐seq analysis on microglia in wild‐type sibling and pde6c mutant retinas at the onset of photoreceptor degeneration (5 dpf) and Müller glia‐mediated neuronal regeneration (4 wpf). At 5 dpf, retinal microglia consist of three clusters, which correspond to homeostatic, degeneration‐response, and stress‐response microglia, respectively. The degeneration‐response cluster expands in pde6c mutants and expresses genes for neuroprotection and tissue repair. At 4 wpf, retinal microglia comprise four clusters, two of which are specifically produced in pde6c mutants and approach the photoreceptor layer. Furthermore, another cluster is prominently localized in the retinal stem cell niche and shows a transcriptomic profile similar to that of neurogenic‐associated microglia (NAM). Comparison of transcriptomic similarity between 4 wpf and 5 dpf microglial clusters revealed that each 4 wpf microglial cluster inherits characteristics of homeostatic, degeneration‐response, and stress‐response state of 5 dpf microglia in different combinations. Thus, there is a unique heterogeneity of microglia in the initial stage of Müller glia‐mediated regeneration. Taken together, our findings reveal a dynamic change of retinal microglia during the transition from photoreceptor degeneration to Müller glia‐mediated neuronal regeneration in zebrafish.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Data links

ncbi.nlm.nih.gov/geo, NCBI; found in “Data Availability Statement”

Data Availability Statement

The data that support the findings of this study are openly available in NCBI's Gene Expression Omnibus (GEO) at https://www.ncbi.nlm.nih.gov/geo/, reference number GSE298347. This will be available after publication.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 2, 28 September 2026

Publisher: n/a → Wiley

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 3 authors, 5 keywords, 10 MeSH terms, 2 funders, 80 references.

Cite

This paper

Ravishankar, D., Takeuchi, Y., & Masai, I. (2026). A Dynamic Change of Microglial States Occurs During the Transition From Photoreceptor Degeneration to Regeneration in Zebrafish pde6c Mutants. Glia, 74(6), e70158. https://doi.org/10.1002/glia.70158

BibTeX

@article{ravishankar2026dynamic, author = {Ravishankar, Darshini and Takeuchi, Yuki and Masai, Ichiro}, title = {{A Dynamic Change of Microglial States Occurs During the Transition From Photoreceptor Degeneration to Regeneration in Zebrafish pde6c Mutants}}, journal = {Glia}, year = {2026}, month = jun, volume = {74}, number = {6}, pages = {e70158}, publisher = {Wiley}, issn = {0894-1491}, doi = {10.1002/glia.70158}, url = {https://doi.org/10.1002/glia.70158}, pmid = {41995141}, pmcid = {PMC13088749} }

RIS

TY - JOUR AU - Ravishankar, Darshini AU - Takeuchi, Yuki AU - Masai, Ichiro TI - A Dynamic Change of Microglial States Occurs During the Transition From Photoreceptor Degeneration to Regeneration in Zebrafish pde6c Mutants T2 - Glia J2 - Glia PY - 2026 DA - 2026/06/01 VL - 74 IS - 6 SP - e70158 SN - 0894-1491 PB - Wiley DO - 10.1002/glia.70158 UR - https://doi.org/10.1002/glia.70158 LA - en ER -

CSL-JSON

{ "id": "10.1002/glia.70158", "type": "article-journal", "title": "A Dynamic Change of Microglial States Occurs During the Transition From Photoreceptor Degeneration to Regeneration in Zebrafish pde6c Mutants", "container-title": "Glia", "author": [ { "family": "Ravishankar", "given": "Darshini" }, { "family": "Takeuchi", "given": "Yuki" }, { "family": "Masai", "given": "Ichiro" } ], "container-title-short": "Glia", "volume": "74", "issue": "6", "page": "e70158", "DOI": "10.1002/glia.70158", "PMID": "41995141", "PMCID": "PMC13088749", "ISSN": "0894-1491", "publisher": "Wiley", "URL": "https://doi.org/10.1002/glia.70158", "language": "en", "issued": { "date-parts": [ [ 2026, 6, 1 ] ] } }

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion, reproductions, activity

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.