Investigation of PANoptosis pathway in age-related macular degeneration triggered by Aβ1-40
Abstract Our study aimed to identify PANoptosis in Aβ1-40-induced AMD, both in vivo and in vitro, and to determine if AIM2-PANoptosome mediates this process. We used transcriptomics to explore the signaling pathways and target genes linked to PANoptosis within a mouse model of AMD triggered by Aβ1-4...
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Nature Portfolio
2025-04-01
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| Online Access: | https://doi.org/10.1038/s41598-025-98174-x |
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| author | Yuxia He Jing Lu Yong Du Long Zhao Lili Gong Ping Wu Qinxin Shu Hui Peng Xing Wang |
| author_facet | Yuxia He Jing Lu Yong Du Long Zhao Lili Gong Ping Wu Qinxin Shu Hui Peng Xing Wang |
| author_sort | Yuxia He |
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| description | Abstract Our study aimed to identify PANoptosis in Aβ1-40-induced AMD, both in vivo and in vitro, and to determine if AIM2-PANoptosome mediates this process. We used transcriptomics to explore the signaling pathways and target genes linked to PANoptosis within a mouse model of AMD triggered by Aβ1-40. Optical coherence tomography (OCT), hematoxylin and eosin (H&E) staining, and electroretinography (ERG) were employed to assess retinal damage in terms of morphology and function. Morphological changes in ARPE-19 cells were observed using optical microscopy and scanning electron microscopy. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of cytokines in cell supernatants, mouse orbital serum, and human plasma to evaluate the severity of inflammation. CO-immunoprecipitation(CoIP) and molecular docking were performed to assess the impact and expression of proteins associated with the AIM2-PANoptosome. Quantitative polymerase chain reaction (qPCR), Western blot (WB), immunofluorescence, and apoptosis detection kits were used to evaluate the expression levels of genes and proteins related to PANoptosis-like cell death. Our results showed that the Aβ1-40-induced AMD model had increased expression of apoptosis, necroptosis, and pyroptosis pathways, and AIM2-PANoptosome components. CoIP and docking confirmed increased AIM2, ZBP1, and PYRIN levels under Aβ1-40 treatment. WB and immunofluorescence showed upregulation of PANoptosis-related proteins. Inhibitors reduced Aβ-induced protein expression. ELISA showed increased inflammatory cytokines. Apoptosis assays and microscopy revealed Aβ1-40-induced ARPE-19 cell loss and morphological changes. In conclusion, the Aβ1-40-induced AMD model displayed PANoptosis-like cell death, offering insights into disease pathogenesis. |
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| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-60e1ef2b1c4a4d829fd496195c3d437b2025-08-20T02:27:53ZengNature PortfolioScientific Reports2045-23222025-04-0115111610.1038/s41598-025-98174-xInvestigation of PANoptosis pathway in age-related macular degeneration triggered by Aβ1-40Yuxia He0Jing Lu1Yong Du2Long Zhao3Lili Gong4Ping Wu5Qinxin Shu6Hui Peng7Xing Wang8Department of Ophthalmology, Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Ophthalmology, Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Ophthalmology, Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Ophthalmology, Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases, The First Affiliated Hospital of Chongqing Medical UniversityGuiyang Aier Eye HospitalDepartment of Ophthalmology, Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Ophthalmology, Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Ophthalmology, Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Ophthalmology, Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases, The First Affiliated Hospital of Chongqing Medical UniversityAbstract Our study aimed to identify PANoptosis in Aβ1-40-induced AMD, both in vivo and in vitro, and to determine if AIM2-PANoptosome mediates this process. We used transcriptomics to explore the signaling pathways and target genes linked to PANoptosis within a mouse model of AMD triggered by Aβ1-40. Optical coherence tomography (OCT), hematoxylin and eosin (H&E) staining, and electroretinography (ERG) were employed to assess retinal damage in terms of morphology and function. Morphological changes in ARPE-19 cells were observed using optical microscopy and scanning electron microscopy. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of cytokines in cell supernatants, mouse orbital serum, and human plasma to evaluate the severity of inflammation. CO-immunoprecipitation(CoIP) and molecular docking were performed to assess the impact and expression of proteins associated with the AIM2-PANoptosome. Quantitative polymerase chain reaction (qPCR), Western blot (WB), immunofluorescence, and apoptosis detection kits were used to evaluate the expression levels of genes and proteins related to PANoptosis-like cell death. Our results showed that the Aβ1-40-induced AMD model had increased expression of apoptosis, necroptosis, and pyroptosis pathways, and AIM2-PANoptosome components. CoIP and docking confirmed increased AIM2, ZBP1, and PYRIN levels under Aβ1-40 treatment. WB and immunofluorescence showed upregulation of PANoptosis-related proteins. Inhibitors reduced Aβ-induced protein expression. ELISA showed increased inflammatory cytokines. Apoptosis assays and microscopy revealed Aβ1-40-induced ARPE-19 cell loss and morphological changes. In conclusion, the Aβ1-40-induced AMD model displayed PANoptosis-like cell death, offering insights into disease pathogenesis.https://doi.org/10.1038/s41598-025-98174-xPANoptosisAge-related macular degeneration (AMD)Amyloid betaInflammation |
| spellingShingle | Yuxia He Jing Lu Yong Du Long Zhao Lili Gong Ping Wu Qinxin Shu Hui Peng Xing Wang Investigation of PANoptosis pathway in age-related macular degeneration triggered by Aβ1-40 Scientific Reports PANoptosis Age-related macular degeneration (AMD) Amyloid beta Inflammation |
| title | Investigation of PANoptosis pathway in age-related macular degeneration triggered by Aβ1-40 |
| title_full | Investigation of PANoptosis pathway in age-related macular degeneration triggered by Aβ1-40 |
| title_fullStr | Investigation of PANoptosis pathway in age-related macular degeneration triggered by Aβ1-40 |
| title_full_unstemmed | Investigation of PANoptosis pathway in age-related macular degeneration triggered by Aβ1-40 |
| title_short | Investigation of PANoptosis pathway in age-related macular degeneration triggered by Aβ1-40 |
| title_sort | investigation of panoptosis pathway in age related macular degeneration triggered by aβ1 40 |
| topic | PANoptosis Age-related macular degeneration (AMD) Amyloid beta Inflammation |
| url | https://doi.org/10.1038/s41598-025-98174-x |
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