Complement C3 deficiency alleviates alkylation-induced retinal degeneration in mice
Abstract Background It has been found that the extensive use of anticancer drugs containing DNA-alkylating agents not only target cancer cells but also cause retinal inflammation through toxic intermediates. Complement C3 (C3) is a core component of the complement activation pathway, and dysregulati...
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | Eye and Vision |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40662-022-00292-4 |
| _version_ | 1811251460830134272 |
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| author | Lu Du Guang-Hua Peng |
| author_facet | Lu Du Guang-Hua Peng |
| author_sort | Lu Du |
| collection | DOAJ |
| description | Abstract Background It has been found that the extensive use of anticancer drugs containing DNA-alkylating agents not only target cancer cells but also cause retinal inflammation through toxic intermediates. Complement C3 (C3) is a core component of the complement activation pathway, and dysregulation of the complement pathway is involved in several retinal degenerative diseases. However, whether C3 plays a critical role in alkylation-induced retinal degeneration is unclear. Methods Following treatment with the alkylating agent methyl methane sulfonate (MMS), the C3 mRNA and protein level was measured, DNA damage and photoreceptor cell death were assessed in both wild-type (WT) C57BL/6J and C3 knockout (KO) mice. Results We determined that complement pathway is activated following MMS treatment, and C3 knockout (KO) increased the rate of photoreceptor cell survival and preserved visual function. The mRNA levels of nuclear erythroid-related factor 2 (Nrf2) and related genes were higher after MMS application in C3 KO mice. Conclusion In summary, our study found that C3 KO promotes photoreceptor cell survival and activates the Nrf2 signaling pathway in the context of alkylation-induced retinal degeneration. |
| first_indexed | 2024-04-12T16:20:49Z |
| format | Article |
| id | doaj.art-454585e7bb8e496c907de7aca2793158 |
| institution | Directory Open Access Journal |
| issn | 2326-0254 |
| language | English |
| last_indexed | 2024-04-12T16:20:49Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Eye and Vision |
| spelling | doaj.art-454585e7bb8e496c907de7aca27931582022-12-22T03:25:34ZengBMCEye and Vision2326-02542022-06-019111010.1186/s40662-022-00292-4Complement C3 deficiency alleviates alkylation-induced retinal degeneration in miceLu Du0Guang-Hua Peng1Department of Ophthalmology, Chinese PLA General HospitalLaboratory of Visual Cell Differentiation and Regulation, Basic Medical College, Zhengzhou UniversityAbstract Background It has been found that the extensive use of anticancer drugs containing DNA-alkylating agents not only target cancer cells but also cause retinal inflammation through toxic intermediates. Complement C3 (C3) is a core component of the complement activation pathway, and dysregulation of the complement pathway is involved in several retinal degenerative diseases. However, whether C3 plays a critical role in alkylation-induced retinal degeneration is unclear. Methods Following treatment with the alkylating agent methyl methane sulfonate (MMS), the C3 mRNA and protein level was measured, DNA damage and photoreceptor cell death were assessed in both wild-type (WT) C57BL/6J and C3 knockout (KO) mice. Results We determined that complement pathway is activated following MMS treatment, and C3 knockout (KO) increased the rate of photoreceptor cell survival and preserved visual function. The mRNA levels of nuclear erythroid-related factor 2 (Nrf2) and related genes were higher after MMS application in C3 KO mice. Conclusion In summary, our study found that C3 KO promotes photoreceptor cell survival and activates the Nrf2 signaling pathway in the context of alkylation-induced retinal degeneration.https://doi.org/10.1186/s40662-022-00292-4Complement C3Retinal degenerationDNA damageApoptosisPhotoreceptor cell |
| spellingShingle | Lu Du Guang-Hua Peng Complement C3 deficiency alleviates alkylation-induced retinal degeneration in mice Eye and Vision Complement C3 Retinal degeneration DNA damage Apoptosis Photoreceptor cell |
| title | Complement C3 deficiency alleviates alkylation-induced retinal degeneration in mice |
| title_full | Complement C3 deficiency alleviates alkylation-induced retinal degeneration in mice |
| title_fullStr | Complement C3 deficiency alleviates alkylation-induced retinal degeneration in mice |
| title_full_unstemmed | Complement C3 deficiency alleviates alkylation-induced retinal degeneration in mice |
| title_short | Complement C3 deficiency alleviates alkylation-induced retinal degeneration in mice |
| title_sort | complement c3 deficiency alleviates alkylation induced retinal degeneration in mice |
| topic | Complement C3 Retinal degeneration DNA damage Apoptosis Photoreceptor cell |
| url | https://doi.org/10.1186/s40662-022-00292-4 |
| work_keys_str_mv | AT ludu complementc3deficiencyalleviatesalkylationinducedretinaldegenerationinmice AT guanghuapeng complementc3deficiencyalleviatesalkylationinducedretinaldegenerationinmice |