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Context-dependent effects of inflammation on retina regeneration

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Abstract

Inflammation is required for the proliferation of Müller glia (MG) into multipotent progenitors (MGPCs) in the injured fish and avian retinas. However, its function in retina regeneration has not been fully understood. Here we investigated the role of inflammation in three different retinal regeneration paradigms in zebrafish (stab-injury, NMDA-injury and insulin treatment). We first show that different types of immune cells and levels of inflammatory cytokines were found in the retinas of these paradigms. Though zymosan injection alone was insufficient to induce MG proliferation in the uninjured retina, immune suppression significantly inhibited MGPC formation in all three paradigms. Enhancing inflammation promoted MGPC formation after stab-injury, while exhibiting a context-dependent role in the NMDA or insulin models. We further show that proper levels of inflammation promoted MG reprogramming and cell cycle re-entry after stab- or NMDA-injury, but excessive inflammation also suppressed MG proliferation in the latter model. Finally, inflammation differentially affected neuronal regeneration in various injury paradigms. Our study reveals the complex and context-dependent role of inflammation during retinal repair in fish and suggests accurate inflammation management may be crucial for successful retina regeneration in mammals.

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Data Availability

The data supporting the results reported in the article are available upon request to the corresponding authors.

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Acknowledgements

We thank the China Zebrafish Resource Center (CZRC) for providing the Tg(mpx:GFP) transgenic zebrafish, and the Institute of Neuroscience, Chinese Academy of Science for sharing the Tg(mpeg1:EGFP) zebrafish.

Funding

National Natural Science Foundation of China (81970820, 31930068), National Key Research and Development Project of China (2017YFA0701304, 2017YFA0104100).

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Author notes

  1. Cuiping Zhou and Xiaoli Zhang both authors contribute equally to this paper

Authors and Affiliations

  1. Key Lab of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, 226001, Jiangsu Province, China

    Cuiping Zhou, Xiaoli Zhang, Yuxi Chen, Zihao Lin, Shuqiang Zhang, Zhiqiang Zhang & Hui Xu

  2. Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China

    Lining Cao & Jianfeng Lu

  3. Eye Institute, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China

    Huaijin Guan

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  1. Cuiping Zhou
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  2. Xiaoli Zhang
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  3. Yuxi Chen
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  4. Zihao Lin
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Contributions

CZ, XZ and YC performed the experiments; CZ, XZ, YC, ZL, SZ, ZZ, LC, HG, JL, and HX analyzed the data; HX designed the experiments and wrote the paper.

Corresponding authors

Correspondence to Jianfeng Lu or Hui Xu.

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All fish used in this study were treated in accordance with the Guidelines for Animal Use and Care at Nantong University.

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The authors declare that they have no competing interests.

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Cite this article

Zhou, C., Zhang, X., Chen, Y. et al. Context-dependent effects of inflammation on retina regeneration. Mol Neurobiol 59, 4351–4367 (2022). https://doi.org/10.1007/s12035-022-02857-9

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  • DOI: https://doi.org/10.1007/s12035-022-02857-9

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