Rac1 overexpression promotes Treg-derived cytokines to mediate choroidal neovascularization in wet age-related macular degeneration
Age-related macular degeneration (AMD), particularly the wet form characterized by choroidal neovascularization, is a leading cause of vision loss. Dysregulation of regulatory T cells (Tregs), key modulators of inflammatory responses, may contribute to wet AMD pathogenesis. This study explored the i...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Associação Brasileira de Divulgação Científica
2025-03-01
|
| Series: | Brazilian Journal of Medical and Biological Research |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2025000100621&lng=en&tlng=en |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850074776973869056 |
|---|---|
| author | Juanjuan Li Yuling Ren Hua Li Zhikun Zheng |
| author_facet | Juanjuan Li Yuling Ren Hua Li Zhikun Zheng |
| author_sort | Juanjuan Li |
| collection | DOAJ |
| description | Age-related macular degeneration (AMD), particularly the wet form characterized by choroidal neovascularization, is a leading cause of vision loss. Dysregulation of regulatory T cells (Tregs), key modulators of inflammatory responses, may contribute to wet AMD pathogenesis. This study explored the involvement of Tregs and the Rac1 signaling pathway in modulating Treg-derived cytokine expression and their role in choroidal neovascularization during wet AMD progression. Peripheral blood samples from healthy controls, dry AMD patients, and wet AMD patients were collected. An in vitro transmembrane co-culture system of Tregs and human choroidal endothelial cells (HCECs) was employed to investigate the impact of Tregs (with or without Rac1 silencing) on the angiogenic phenotype of HCECs. A mouse model of AMD was established to evaluate the effects of a Rac1 inhibitor and IL-10/TGF-β neutralization on Tregs and choroidal neovascularization. An increased Treg percentage in the CD4+ T lymphocyte population was found in the peripheral blood samples of wet AMD patients. Tregs from wet AMD patients showed an increased expression of Rac1 and an elevated production of IL-10 and TGF-β1. Rac1 silencing suppressed Treg stability and differentiation, and impaired the pro-angiogenic effect of Tregs on HCECs. In the animal model of AMD, the administration of a Rac1 inhibitor or neutralizing antibodies against IL-10/TGF-β1 reduced Treg abundance and attenuated choroidal neovascularization. Rac1 upregulation in Tregs promoted IL-10 and TGF-β1 production to mediate choroidal neovascularization in wet AMD. Targeting Rac1 and Treg-derived IL-10/TGF-β1 production in Tregs may serve as a strategy to ameliorate AMD progression. |
| format | Article |
| id | doaj-art-a6f32b648c0c472dbb866e3e6fecad9a |
| institution | DOAJ |
| issn | 1414-431X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj-art-a6f32b648c0c472dbb866e3e6fecad9a2025-08-20T02:46:29ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research1414-431X2025-03-015810.1590/1414-431x2024e14187Rac1 overexpression promotes Treg-derived cytokines to mediate choroidal neovascularization in wet age-related macular degenerationJuanjuan Lihttps://orcid.org/0000-0003-0023-7895Yuling Renhttps://orcid.org/0000-0002-3120-2225Hua Lihttps://orcid.org/0009-0007-6147-0574Zhikun Zhenghttps://orcid.org/0009-0000-1394-7971Age-related macular degeneration (AMD), particularly the wet form characterized by choroidal neovascularization, is a leading cause of vision loss. Dysregulation of regulatory T cells (Tregs), key modulators of inflammatory responses, may contribute to wet AMD pathogenesis. This study explored the involvement of Tregs and the Rac1 signaling pathway in modulating Treg-derived cytokine expression and their role in choroidal neovascularization during wet AMD progression. Peripheral blood samples from healthy controls, dry AMD patients, and wet AMD patients were collected. An in vitro transmembrane co-culture system of Tregs and human choroidal endothelial cells (HCECs) was employed to investigate the impact of Tregs (with or without Rac1 silencing) on the angiogenic phenotype of HCECs. A mouse model of AMD was established to evaluate the effects of a Rac1 inhibitor and IL-10/TGF-β neutralization on Tregs and choroidal neovascularization. An increased Treg percentage in the CD4+ T lymphocyte population was found in the peripheral blood samples of wet AMD patients. Tregs from wet AMD patients showed an increased expression of Rac1 and an elevated production of IL-10 and TGF-β1. Rac1 silencing suppressed Treg stability and differentiation, and impaired the pro-angiogenic effect of Tregs on HCECs. In the animal model of AMD, the administration of a Rac1 inhibitor or neutralizing antibodies against IL-10/TGF-β1 reduced Treg abundance and attenuated choroidal neovascularization. Rac1 upregulation in Tregs promoted IL-10 and TGF-β1 production to mediate choroidal neovascularization in wet AMD. Targeting Rac1 and Treg-derived IL-10/TGF-β1 production in Tregs may serve as a strategy to ameliorate AMD progression.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2025000100621&lng=en&tlng=enAge-related macular degeneration (AMD)Regulatory T cells (Tregs)Choroidal neovascularizationAngiogenesisRac1 |
| spellingShingle | Juanjuan Li Yuling Ren Hua Li Zhikun Zheng Rac1 overexpression promotes Treg-derived cytokines to mediate choroidal neovascularization in wet age-related macular degeneration Brazilian Journal of Medical and Biological Research Age-related macular degeneration (AMD) Regulatory T cells (Tregs) Choroidal neovascularization Angiogenesis Rac1 |
| title | Rac1 overexpression promotes Treg-derived cytokines to mediate choroidal neovascularization in wet age-related macular degeneration |
| title_full | Rac1 overexpression promotes Treg-derived cytokines to mediate choroidal neovascularization in wet age-related macular degeneration |
| title_fullStr | Rac1 overexpression promotes Treg-derived cytokines to mediate choroidal neovascularization in wet age-related macular degeneration |
| title_full_unstemmed | Rac1 overexpression promotes Treg-derived cytokines to mediate choroidal neovascularization in wet age-related macular degeneration |
| title_short | Rac1 overexpression promotes Treg-derived cytokines to mediate choroidal neovascularization in wet age-related macular degeneration |
| title_sort | rac1 overexpression promotes treg derived cytokines to mediate choroidal neovascularization in wet age related macular degeneration |
| topic | Age-related macular degeneration (AMD) Regulatory T cells (Tregs) Choroidal neovascularization Angiogenesis Rac1 |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2025000100621&lng=en&tlng=en |
| work_keys_str_mv | AT juanjuanli rac1overexpressionpromotestregderivedcytokinestomediatechoroidalneovascularizationinwetagerelatedmaculardegeneration AT yulingren rac1overexpressionpromotestregderivedcytokinestomediatechoroidalneovascularizationinwetagerelatedmaculardegeneration AT huali rac1overexpressionpromotestregderivedcytokinestomediatechoroidalneovascularizationinwetagerelatedmaculardegeneration AT zhikunzheng rac1overexpressionpromotestregderivedcytokinestomediatechoroidalneovascularizationinwetagerelatedmaculardegeneration |