Melatonin protects retinal integrity through mediated immune homeostasis in the sodium iodate-induced mouse model of age-related macular degeneration

• Published in: Biomedicine & pharmacotherapy Vol. 161; p. 114476
• Main Authors: Ku, Li-Cheng, Sheu, Meei-Ling, Cheng, He-Hsiung, Lee, Chun-Yi, Tsai, Yi-Ching, Tsai, Chia-Yun, Lin, Keng-Hung, Lai, Lih-Ching, Lai, De-Wei
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.05.2023; Elsevier
• Subjects: Age-related macular degeneration; Aged; Animals; Disease Models, Animal; Homeostasis; Humans; Macular Degeneration - chemically induced; Macular Degeneration - genetics; Melatonin; Melatonin - metabolism; Melatonin - pharmacology; Mice; Regulatory T cells; Retina - pathology; Retinal Pigment Epithelium; ENTPD1; Melatonin; Tregs; RPE; MT; ASMT; TET2; Regulatory T cells; TPH; NT5E; Age-related macular degeneration; AMD; CCR4
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2023.114476

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. 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. 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. 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. [Display omitted] •Melatonin can effectively ameliorate retinal degeneration in the sodium iodate(NaIO3)-induced retinal degeneration mouse model is first confirmed to regulate immune homeostasis via Tregs.•Melatonin, as a potential regulator of retinal degeneration, was investigated by using both immunofluorescence staining in whole- mounting the retina tissue and methylation assay in Tregs for the first time.•NT5E/TET2 pathway in Tregs could be a possible anti-retinal degeneration response mechanism for Melatonin treatment.•Melatonin might be a potential modulation of the immune response may provide a key therapeutic strategy to aid the regeneration of retinal degeneration or a strategy in preventive medicine.