Effects of different alkylating agents on photoreceptor degeneration and proliferative response of Müller glia
Abstract Animal models for retinal degeneration are essential for elucidating its pathogenesis and developing new therapeutic strategies in humans. N-methyl-N-nitrosourea (MNU) has been extensively used to construct a photoreceptor-specific degeneration model, which has served to unveil the molecula...
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-50485-7 |
| _version_ | 1797363438938226688 |
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| author | Kaori Nomura-Komoike Reiko Nishino Hiroki Fujieda |
| author_facet | Kaori Nomura-Komoike Reiko Nishino Hiroki Fujieda |
| author_sort | Kaori Nomura-Komoike |
| collection | DOAJ |
| description | Abstract Animal models for retinal degeneration are essential for elucidating its pathogenesis and developing new therapeutic strategies in humans. N-methyl-N-nitrosourea (MNU) has been extensively used to construct a photoreceptor-specific degeneration model, which has served to unveil the molecular process of photoreceptor degeneration as well as the mechanisms regulating the protective responses of remaining cells. Methyl methanesulphonate (MMS), also known to cause photoreceptor degeneration, is considered a good alternative to MNU due to its higher usability; however, detailed pathophysiological processes after MMS treatment remain uncharacterized. Here, we analyzed the time course of photoreceptor degeneration, Müller glial proliferation, and expression of secretory factors after MNU and MMS treatments in rats. While the timing of rod degeneration was similar between the treatments, we unexpectedly found that cones survived slightly longer after MMS treatment. Müller glia reentered the cell cycle at a similar timing after the two treatments; however, the G1/S transition occurred earlier after MMS treatment. Moreover, growth factors such as FGF2 and LIF were more highly upregulated in the MMS model. These data suggest that comparative analyses of the two injury models may be beneficial for understanding the complex regulatory mechanisms underlying the proliferative response of Müller glia. |
| first_indexed | 2024-03-08T16:21:23Z |
| format | Article |
| id | doaj.art-54ee52390375433684b8ca8f86e10137 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-08T16:21:23Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-54ee52390375433684b8ca8f86e101372024-01-07T12:19:21ZengNature PortfolioScientific Reports2045-23222024-01-0114111010.1038/s41598-023-50485-7Effects of different alkylating agents on photoreceptor degeneration and proliferative response of Müller gliaKaori Nomura-Komoike0Reiko Nishino1Hiroki Fujieda2Department of Anatomy and Neurobiology, School of Medicine, Tokyo Women’s Medical UniversityDepartment of Anatomy and Neurobiology, School of Medicine, Tokyo Women’s Medical UniversityDepartment of Anatomy and Neurobiology, School of Medicine, Tokyo Women’s Medical UniversityAbstract Animal models for retinal degeneration are essential for elucidating its pathogenesis and developing new therapeutic strategies in humans. N-methyl-N-nitrosourea (MNU) has been extensively used to construct a photoreceptor-specific degeneration model, which has served to unveil the molecular process of photoreceptor degeneration as well as the mechanisms regulating the protective responses of remaining cells. Methyl methanesulphonate (MMS), also known to cause photoreceptor degeneration, is considered a good alternative to MNU due to its higher usability; however, detailed pathophysiological processes after MMS treatment remain uncharacterized. Here, we analyzed the time course of photoreceptor degeneration, Müller glial proliferation, and expression of secretory factors after MNU and MMS treatments in rats. While the timing of rod degeneration was similar between the treatments, we unexpectedly found that cones survived slightly longer after MMS treatment. Müller glia reentered the cell cycle at a similar timing after the two treatments; however, the G1/S transition occurred earlier after MMS treatment. Moreover, growth factors such as FGF2 and LIF were more highly upregulated in the MMS model. These data suggest that comparative analyses of the two injury models may be beneficial for understanding the complex regulatory mechanisms underlying the proliferative response of Müller glia.https://doi.org/10.1038/s41598-023-50485-7 |
| spellingShingle | Kaori Nomura-Komoike Reiko Nishino Hiroki Fujieda Effects of different alkylating agents on photoreceptor degeneration and proliferative response of Müller glia Scientific Reports |
| title | Effects of different alkylating agents on photoreceptor degeneration and proliferative response of Müller glia |
| title_full | Effects of different alkylating agents on photoreceptor degeneration and proliferative response of Müller glia |
| title_fullStr | Effects of different alkylating agents on photoreceptor degeneration and proliferative response of Müller glia |
| title_full_unstemmed | Effects of different alkylating agents on photoreceptor degeneration and proliferative response of Müller glia |
| title_short | Effects of different alkylating agents on photoreceptor degeneration and proliferative response of Müller glia |
| title_sort | effects of different alkylating agents on photoreceptor degeneration and proliferative response of muller glia |
| url | https://doi.org/10.1038/s41598-023-50485-7 |
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