Absent in melanoma 2: a potent suppressor of retinal pigment epithelial-mesenchymal transition and experimental proliferative vitreoretinopathy
Abstract Epithelial-to-mesenchymal transition (EMT) is a critical and complex process involved in normal embryonic development, tissue regeneration, and tumor progression. It also contributes to retinal diseases, such as age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR...
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Nature Publishing Group
2025-01-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07367-9 |
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| author | Yu Chen Mingyuan Jiang Liping Li Shanshan Yang Zuimeng Liu Shiwen Lin Wanxiao Wang Jinyang Li Feng Chen Qiang Hou Xiaoyin Ma Ling Hou |
| author_facet | Yu Chen Mingyuan Jiang Liping Li Shanshan Yang Zuimeng Liu Shiwen Lin Wanxiao Wang Jinyang Li Feng Chen Qiang Hou Xiaoyin Ma Ling Hou |
| author_sort | Yu Chen |
| collection | DOAJ |
| description | Abstract Epithelial-to-mesenchymal transition (EMT) is a critical and complex process involved in normal embryonic development, tissue regeneration, and tumor progression. It also contributes to retinal diseases, such as age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR). Although absent in melanoma 2 (AIM2) has been linked to inflammatory disorders, autoimmune diseases, and cancers, its role in the EMT of the retinal pigment epithelium (RPE-EMT) and retinal diseases remains unclear. The present study demonstrated that AIM2 functions as a potent suppressor of RPE cell proliferation and EMT to maintain retinal homeostasis. Transcriptome analysis using RNA-sequencing (RNA-Seq) revealed that AIM2 was significantly downregulated in primary human RPE (phRPE) cells undergoing EMT and proliferation. Consequently, Aim2-deficient mice showed morphological changes and increased FN expression in RPE cells under physiological conditions, whereas AIM2 overexpression in phRPE cells inhibited EMT. In a retinal detachment-induced PVR mouse model, AIM2 deficiency promotes RPE-EMT, resulting in severe experimental PVR. Clinical samples further confirmed the downregulation of AIM2 in the PVR membranes from patients. Kyoto Encyclopedia of Genes and Genome analysis revealed that the PI3K-AKT signaling pathway was significantly related to RPE-EMT and that AIM2 inhibited AKT activation in RPE cells by reducing its phosphorylation. Moreover, treatment with eye drops containing an AKT inhibitor alleviated RPE-EMT and the severity of experimental PVR. These findings provide new insights into the complex mechanisms underlying RPE-EMT and PVR pathogenesis, with implications for rational strategies for potential therapeutic applications in PVR by targeting RPE-EMT. |
| format | Article |
| id | doaj-art-4d340d0ca96b49f09ca8eb08b5019e1d |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-4d340d0ca96b49f09ca8eb08b5019e1d2025-02-02T12:44:47ZengNature Publishing GroupCell Death and Disease2041-48892025-01-0116111310.1038/s41419-025-07367-9Absent in melanoma 2: a potent suppressor of retinal pigment epithelial-mesenchymal transition and experimental proliferative vitreoretinopathyYu Chen0Mingyuan Jiang1Liping Li2Shanshan Yang3Zuimeng Liu4Shiwen Lin5Wanxiao Wang6Jinyang Li7Feng Chen8Qiang Hou9Xiaoyin Ma10Ling Hou11Laboratory of Developmental Cell Biology and Disease, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityLaboratory of Developmental Cell Biology and Disease, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityLaboratory of Developmental Cell Biology and Disease, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityLaboratory of Developmental Cell Biology and Disease, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityLaboratory of Developmental Cell Biology and Disease, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityLaboratory of Developmental Cell Biology and Disease, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityLaboratory of Developmental Cell Biology and Disease, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityNational Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityNational Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityState Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityLaboratory of Developmental Cell Biology and Disease, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityLaboratory of Developmental Cell Biology and Disease, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical UniversityAbstract Epithelial-to-mesenchymal transition (EMT) is a critical and complex process involved in normal embryonic development, tissue regeneration, and tumor progression. It also contributes to retinal diseases, such as age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR). Although absent in melanoma 2 (AIM2) has been linked to inflammatory disorders, autoimmune diseases, and cancers, its role in the EMT of the retinal pigment epithelium (RPE-EMT) and retinal diseases remains unclear. The present study demonstrated that AIM2 functions as a potent suppressor of RPE cell proliferation and EMT to maintain retinal homeostasis. Transcriptome analysis using RNA-sequencing (RNA-Seq) revealed that AIM2 was significantly downregulated in primary human RPE (phRPE) cells undergoing EMT and proliferation. Consequently, Aim2-deficient mice showed morphological changes and increased FN expression in RPE cells under physiological conditions, whereas AIM2 overexpression in phRPE cells inhibited EMT. In a retinal detachment-induced PVR mouse model, AIM2 deficiency promotes RPE-EMT, resulting in severe experimental PVR. Clinical samples further confirmed the downregulation of AIM2 in the PVR membranes from patients. Kyoto Encyclopedia of Genes and Genome analysis revealed that the PI3K-AKT signaling pathway was significantly related to RPE-EMT and that AIM2 inhibited AKT activation in RPE cells by reducing its phosphorylation. Moreover, treatment with eye drops containing an AKT inhibitor alleviated RPE-EMT and the severity of experimental PVR. These findings provide new insights into the complex mechanisms underlying RPE-EMT and PVR pathogenesis, with implications for rational strategies for potential therapeutic applications in PVR by targeting RPE-EMT.https://doi.org/10.1038/s41419-025-07367-9 |
| spellingShingle | Yu Chen Mingyuan Jiang Liping Li Shanshan Yang Zuimeng Liu Shiwen Lin Wanxiao Wang Jinyang Li Feng Chen Qiang Hou Xiaoyin Ma Ling Hou Absent in melanoma 2: a potent suppressor of retinal pigment epithelial-mesenchymal transition and experimental proliferative vitreoretinopathy Cell Death and Disease |
| title | Absent in melanoma 2: a potent suppressor of retinal pigment epithelial-mesenchymal transition and experimental proliferative vitreoretinopathy |
| title_full | Absent in melanoma 2: a potent suppressor of retinal pigment epithelial-mesenchymal transition and experimental proliferative vitreoretinopathy |
| title_fullStr | Absent in melanoma 2: a potent suppressor of retinal pigment epithelial-mesenchymal transition and experimental proliferative vitreoretinopathy |
| title_full_unstemmed | Absent in melanoma 2: a potent suppressor of retinal pigment epithelial-mesenchymal transition and experimental proliferative vitreoretinopathy |
| title_short | Absent in melanoma 2: a potent suppressor of retinal pigment epithelial-mesenchymal transition and experimental proliferative vitreoretinopathy |
| title_sort | absent in melanoma 2 a potent suppressor of retinal pigment epithelial mesenchymal transition and experimental proliferative vitreoretinopathy |
| url | https://doi.org/10.1038/s41419-025-07367-9 |
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