Melatonin protects retinal integrity through mediated immune homeostasis in the sodium iodate-induced mouse model of age-related macular degeneration
Background: Age-related macular degeneration is the leading cause of visual deficiency in older adults worldwide. Melatonin (MT) can potentially reduce retinal deterioration. However, the mechanism by which MT mediates regulatory T cells (Tregs) in the retina is not yet fully understood. Methods: Th...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223002640 |
| _version_ | 1797857679814688768 |
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| author | Li-Cheng Ku Meei-Ling Sheu He-Hsiung Cheng Chun-Yi Lee Yi-Ching Tsai Chia-Yun Tsai Keng-Hung Lin Lih-Ching Lai De-Wei Lai |
| author_facet | Li-Cheng Ku Meei-Ling Sheu He-Hsiung Cheng Chun-Yi Lee Yi-Ching Tsai Chia-Yun Tsai Keng-Hung Lin Lih-Ching Lai De-Wei Lai |
| author_sort | Li-Cheng Ku |
| collection | DOAJ |
| description | Background: Age-related macular degeneration is the leading cause of visual deficiency in older adults worldwide. Melatonin (MT) can potentially reduce retinal deterioration. However, the mechanism by which MT mediates regulatory T cells (Tregs) in the retina is not yet fully understood. Methods: The transcriptome profiles of aged or young human retinal tissues from the GEO database were analyzed for MT-related gene expression. The pathological changes in the retina in the NaIO3-induced mouse model were quantitatively determined by staining with hematoxylin and eosin. Retinal whole-mounting immunofluorescence staining was conducted to determine the expression of the Treg-specific marker FOXP3. The phenotypes of M1/M2 macrophages were representing related gene markers in the retina. The GEO database includes biopsies from patients with retinal detachment for ENPTD1, NT5E, and TET2 gene expression. A pyrosequencing assay was performed for NT5E DNA methylation on human primary Tregs, and siTET2 transfection engineering was used. Results: MT synthesis-related genes in retinal tissue may be affected by age. Our study shows that MT can effectively restore NaIO3-induced retinopathy and maintain retinal structural integrity. Importantly, MT may assist the conversion of M1 to M2 macrophages to promote tissue repair, which may be caused by the increased infiltration of Tregs. Moreover, MT treatment may upregulate TET2, and further NT5E demethylation is associated with Treg recruitment in the retinal microenvironment. Conclusions: Our findings suggest that MT can effectively ameliorate retinal degeneration and regulate immune homeostasis via Tregs. Modulation of the immune response may provide a key therapeutic strategy. |
| first_indexed | 2024-04-09T21:01:45Z |
| format | Article |
| id | doaj.art-50fac308ad7d49a09b95ecd40ab49f88 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-09T21:01:45Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-50fac308ad7d49a09b95ecd40ab49f882023-03-29T09:22:36ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-05-01161114476Melatonin protects retinal integrity through mediated immune homeostasis in the sodium iodate-induced mouse model of age-related macular degenerationLi-Cheng Ku0Meei-Ling Sheu1He-Hsiung Cheng2Chun-Yi Lee3Yi-Ching Tsai4Chia-Yun Tsai5Keng-Hung Lin6Lih-Ching Lai7De-Wei Lai8Taichung Veterans General Hospital, Taichung, TaiwanInstitute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan, Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan, Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, TaiwanDivision of Allergy, Immunology and Rheumatology, Chang Bing Show Chwan Memorial Hospital, Changhua, TaiwanDepartment of Pediatrics, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan, Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanDepartment of Immune Medicine, Chang Bing Show Chwan Memorial Hospital, Changhua, TaiwanExperimental Animal Center, Department of Molecular Biology and Cell Research, Chang Bing Show Chwan Memorial Hospital, Changhua, TaiwanRong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan; Department of Ophthalmology, Taichung Veterans General Hospital, Taiwan, National Chung Hsing University, Taichung, TaiwanDepartment of Ophthalmology, Chang Bing Show Chwan Memorial Hospital, Changhua, TaiwanExperimental Animal Center, Department of Molecular Biology and Cell Research, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan; Department of Nursing, Central Taiwan University of Science and Technology, Taichung, Taiwan; Department of Pharmacy and Master Program, Tajen University, Pingtung, Taiwan; Correspondence to: 3F, Research Building, No. 6, Lugong Rd., Lukang Township, Changhua County 505, 811586, Taiwan ROCBackground: Age-related macular degeneration is the leading cause of visual deficiency in older adults worldwide. Melatonin (MT) can potentially reduce retinal deterioration. However, the mechanism by which MT mediates regulatory T cells (Tregs) in the retina is not yet fully understood. Methods: The transcriptome profiles of aged or young human retinal tissues from the GEO database were analyzed for MT-related gene expression. The pathological changes in the retina in the NaIO3-induced mouse model were quantitatively determined by staining with hematoxylin and eosin. Retinal whole-mounting immunofluorescence staining was conducted to determine the expression of the Treg-specific marker FOXP3. The phenotypes of M1/M2 macrophages were representing related gene markers in the retina. The GEO database includes biopsies from patients with retinal detachment for ENPTD1, NT5E, and TET2 gene expression. A pyrosequencing assay was performed for NT5E DNA methylation on human primary Tregs, and siTET2 transfection engineering was used. Results: MT synthesis-related genes in retinal tissue may be affected by age. Our study shows that MT can effectively restore NaIO3-induced retinopathy and maintain retinal structural integrity. Importantly, MT may assist the conversion of M1 to M2 macrophages to promote tissue repair, which may be caused by the increased infiltration of Tregs. Moreover, MT treatment may upregulate TET2, and further NT5E demethylation is associated with Treg recruitment in the retinal microenvironment. Conclusions: Our findings suggest that MT can effectively ameliorate retinal degeneration and regulate immune homeostasis via Tregs. Modulation of the immune response may provide a key therapeutic strategy.http://www.sciencedirect.com/science/article/pii/S0753332223002640Age-related macular degenerationMelatoninRegulatory T cells |
| spellingShingle | Li-Cheng Ku Meei-Ling Sheu He-Hsiung Cheng Chun-Yi Lee Yi-Ching Tsai Chia-Yun Tsai Keng-Hung Lin Lih-Ching Lai De-Wei Lai Melatonin protects retinal integrity through mediated immune homeostasis in the sodium iodate-induced mouse model of age-related macular degeneration Biomedicine & Pharmacotherapy Age-related macular degeneration Melatonin Regulatory T cells |
| title | Melatonin protects retinal integrity through mediated immune homeostasis in the sodium iodate-induced mouse model of age-related macular degeneration |
| title_full | Melatonin protects retinal integrity through mediated immune homeostasis in the sodium iodate-induced mouse model of age-related macular degeneration |
| title_fullStr | Melatonin protects retinal integrity through mediated immune homeostasis in the sodium iodate-induced mouse model of age-related macular degeneration |
| title_full_unstemmed | Melatonin protects retinal integrity through mediated immune homeostasis in the sodium iodate-induced mouse model of age-related macular degeneration |
| title_short | Melatonin protects retinal integrity through mediated immune homeostasis in the sodium iodate-induced mouse model of age-related macular degeneration |
| title_sort | melatonin protects retinal integrity through mediated immune homeostasis in the sodium iodate induced mouse model of age related macular degeneration |
| topic | Age-related macular degeneration Melatonin Regulatory T cells |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223002640 |
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