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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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-04-01
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| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-98174-x |
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| Summary: | 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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| ISSN: | 2045-2322 |