Complement C3a receptor inactivation attenuates retinal degeneration induced by oxidative damage
Retinal degeneration causes vision loss and threatens the health of elderly individuals worldwide. Evidence indicates that the activation of the complement system is associated with retinal degeneration. However, the mechanism of complement signaling in retinal degeneration needs to be further studi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2022.951491/full |
| _version_ | 1828746211219210240 |
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| author | Shaojun Wang Lu Du Shunzong Yuan Guang-Hua Peng Guang-Hua Peng |
| author_facet | Shaojun Wang Lu Du Shunzong Yuan Guang-Hua Peng Guang-Hua Peng |
| author_sort | Shaojun Wang |
| collection | DOAJ |
| description | Retinal degeneration causes vision loss and threatens the health of elderly individuals worldwide. Evidence indicates that the activation of the complement system is associated with retinal degeneration. However, the mechanism of complement signaling in retinal degeneration needs to be further studied. In this study, we show that the expression of C3 and C3a receptor (C3ar1) is positively associated with the inflammatory response and retinal degeneration. Genetic deletion of C3 and pharmacological inhibition of C3ar1 resulted in the alleviation of neuroinflammation, prevention of photoreceptor cell apoptosis and restoration of visual function. RNA sequencing (RNA-seq) identified a C3ar1-dependent network shown to regulate microglial activation and astrocyte gliosis formation. Mechanistically, we found that STAT3 functioned downstream of the C3-C3ar1 pathway and that the C3ar1-STAT3 pathway functionally mediated the immune response and photoreceptor cell degeneration in response to oxidative stress. These findings reveal an important role of C3ar1 in oxidative-induced retinal degeneration and suggest that intervention of the C3ar1 pathway may alleviate retinal degeneration. |
| first_indexed | 2024-04-14T04:20:21Z |
| format | Article |
| id | doaj.art-046c6721f954451389d27dc7b2abd19a |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-14T04:20:21Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neuroscience |
| spelling | doaj.art-046c6721f954451389d27dc7b2abd19a2022-12-22T02:12:34ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2022-08-011610.3389/fnins.2022.951491951491Complement C3a receptor inactivation attenuates retinal degeneration induced by oxidative damageShaojun Wang0Lu Du1Shunzong Yuan2Guang-Hua Peng3Guang-Hua Peng4Senior Department of Ophthalmology, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, ChinaSenior Department of Ophthalmology, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, ChinaDepartment of Lymphoma, Head and Neck Cancer, The Fifth Medical Center, Chinese People’s Liberation Army (PLA) General Hospital (Former 307th Hospital of the PLA), Beijing, ChinaLaboratory of Visual Cell Differentiation and Regulation, Basic Medical College, Zhengzhou University, Zhengzhou, ChinaDepartment of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, ChinaRetinal degeneration causes vision loss and threatens the health of elderly individuals worldwide. Evidence indicates that the activation of the complement system is associated with retinal degeneration. However, the mechanism of complement signaling in retinal degeneration needs to be further studied. In this study, we show that the expression of C3 and C3a receptor (C3ar1) is positively associated with the inflammatory response and retinal degeneration. Genetic deletion of C3 and pharmacological inhibition of C3ar1 resulted in the alleviation of neuroinflammation, prevention of photoreceptor cell apoptosis and restoration of visual function. RNA sequencing (RNA-seq) identified a C3ar1-dependent network shown to regulate microglial activation and astrocyte gliosis formation. Mechanistically, we found that STAT3 functioned downstream of the C3-C3ar1 pathway and that the C3ar1-STAT3 pathway functionally mediated the immune response and photoreceptor cell degeneration in response to oxidative stress. These findings reveal an important role of C3ar1 in oxidative-induced retinal degeneration and suggest that intervention of the C3ar1 pathway may alleviate retinal degeneration.https://www.frontiersin.org/articles/10.3389/fnins.2022.951491/fullcomplement C3C3a receptor (C3ar1)retinal degenerationapoptosismicroglia |
| spellingShingle | Shaojun Wang Lu Du Shunzong Yuan Guang-Hua Peng Guang-Hua Peng Complement C3a receptor inactivation attenuates retinal degeneration induced by oxidative damage Frontiers in Neuroscience complement C3 C3a receptor (C3ar1) retinal degeneration apoptosis microglia |
| title | Complement C3a receptor inactivation attenuates retinal degeneration induced by oxidative damage |
| title_full | Complement C3a receptor inactivation attenuates retinal degeneration induced by oxidative damage |
| title_fullStr | Complement C3a receptor inactivation attenuates retinal degeneration induced by oxidative damage |
| title_full_unstemmed | Complement C3a receptor inactivation attenuates retinal degeneration induced by oxidative damage |
| title_short | Complement C3a receptor inactivation attenuates retinal degeneration induced by oxidative damage |
| title_sort | complement c3a receptor inactivation attenuates retinal degeneration induced by oxidative damage |
| topic | complement C3 C3a receptor (C3ar1) retinal degeneration apoptosis microglia |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2022.951491/full |
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