Vasoactive intestinal peptide reduces ocular hypertension by regulating tight junction of trabecular meshwork through Rab13/PKA signalling complex
Background Schlemm’s canal and trabecular meshwork (TM) are conventional outflow pathway of aqueous humour, which play an important role in maintaining intraocular pressure (IOP) homeostasis. Our previous research has implied that vasoactive intestinal peptide (VIP) reduces high IOP by regulating th...
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Taylor & Francis Group
2025-12-01
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| Series: | Annals of Medicine |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/07853890.2025.2534527 |
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| author | Liwen Chen Xiaoqin Yan Zhaoxia Luo Yang Cheng Mu Li |
| author_facet | Liwen Chen Xiaoqin Yan Zhaoxia Luo Yang Cheng Mu Li |
| author_sort | Liwen Chen |
| collection | DOAJ |
| description | Background Schlemm’s canal and trabecular meshwork (TM) are conventional outflow pathway of aqueous humour, which play an important role in maintaining intraocular pressure (IOP) homeostasis. Our previous research has implied that vasoactive intestinal peptide (VIP) reduces high IOP by regulating the distribution of F-actin in the endothelial cells of Schlemm’s canal. In this study, we investigated the mechanism by which VIP affects tight junction (TJ) of TM.Methods Burning three episcleral veins in the eye of rats and pressure-stimulating human trabecular meshwork cells (HTMCs) were respectively employed to establish high IOP animal and cell models. The IOP of the rats was measured by TonoLab during the period of 1–2 min after isoflurane anaesthesia at 10:00 to 11:00 a.m. on the measurement day. The tissue density of TM was observed by haematoxylin–eosin staining. Western blotting, qRT-PCR, immunofluorescence and immunohistochemistry were utilized to assess the levels of ZO-1, Claudin-1, Rab13 and PKA in TM tissue or cells.Results The expression of TJ-related proteins ZO-1 and Claudin-1 increased significantly in high IOP rat models and pressure-stimulated HTMCs. Furthermore, both VIP and the overexpression of Rab13 reduced the expression of TJ-related proteins ZO-1 and Claudin-1 in pressure-stimulated HTMCs. However, the knockdown of Rab13 reversed the effect of VIP on TJ in vitro. In high IOP rat models, VIP reduced the expression of TJ-related proteins ZO-1 and Claudin-1 and the tissue density of TM, thereby reducing ocular hypertension.Conclusions VIP inhibited TJ of TM cells by regulating the Rab13–PKA signalling complex, leading to the reduction of ocular hypertension in rats. This study provides new sights for the treatment of ocular hypertension. |
| format | Article |
| id | doaj-art-b926e54bcc474a0eb9e66d77037fe546 |
| institution | Kabale University |
| issn | 0785-3890 1365-2060 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
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| series | Annals of Medicine |
| spelling | doaj-art-b926e54bcc474a0eb9e66d77037fe5462025-08-20T03:56:42ZengTaylor & Francis GroupAnnals of Medicine0785-38901365-20602025-12-0157110.1080/07853890.2025.2534527Vasoactive intestinal peptide reduces ocular hypertension by regulating tight junction of trabecular meshwork through Rab13/PKA signalling complexLiwen Chen0Xiaoqin Yan1Zhaoxia Luo2Yang Cheng3Mu Li4Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaBackground Schlemm’s canal and trabecular meshwork (TM) are conventional outflow pathway of aqueous humour, which play an important role in maintaining intraocular pressure (IOP) homeostasis. Our previous research has implied that vasoactive intestinal peptide (VIP) reduces high IOP by regulating the distribution of F-actin in the endothelial cells of Schlemm’s canal. In this study, we investigated the mechanism by which VIP affects tight junction (TJ) of TM.Methods Burning three episcleral veins in the eye of rats and pressure-stimulating human trabecular meshwork cells (HTMCs) were respectively employed to establish high IOP animal and cell models. The IOP of the rats was measured by TonoLab during the period of 1–2 min after isoflurane anaesthesia at 10:00 to 11:00 a.m. on the measurement day. The tissue density of TM was observed by haematoxylin–eosin staining. Western blotting, qRT-PCR, immunofluorescence and immunohistochemistry were utilized to assess the levels of ZO-1, Claudin-1, Rab13 and PKA in TM tissue or cells.Results The expression of TJ-related proteins ZO-1 and Claudin-1 increased significantly in high IOP rat models and pressure-stimulated HTMCs. Furthermore, both VIP and the overexpression of Rab13 reduced the expression of TJ-related proteins ZO-1 and Claudin-1 in pressure-stimulated HTMCs. However, the knockdown of Rab13 reversed the effect of VIP on TJ in vitro. In high IOP rat models, VIP reduced the expression of TJ-related proteins ZO-1 and Claudin-1 and the tissue density of TM, thereby reducing ocular hypertension.Conclusions VIP inhibited TJ of TM cells by regulating the Rab13–PKA signalling complex, leading to the reduction of ocular hypertension in rats. This study provides new sights for the treatment of ocular hypertension.https://www.tandfonline.com/doi/10.1080/07853890.2025.2534527Ocular hypertensionvasoactive intestinal peptidetight junctiontrabecular meshworkRab13–PKA signalling complex |
| spellingShingle | Liwen Chen Xiaoqin Yan Zhaoxia Luo Yang Cheng Mu Li Vasoactive intestinal peptide reduces ocular hypertension by regulating tight junction of trabecular meshwork through Rab13/PKA signalling complex Annals of Medicine Ocular hypertension vasoactive intestinal peptide tight junction trabecular meshwork Rab13–PKA signalling complex |
| title | Vasoactive intestinal peptide reduces ocular hypertension by regulating tight junction of trabecular meshwork through Rab13/PKA signalling complex |
| title_full | Vasoactive intestinal peptide reduces ocular hypertension by regulating tight junction of trabecular meshwork through Rab13/PKA signalling complex |
| title_fullStr | Vasoactive intestinal peptide reduces ocular hypertension by regulating tight junction of trabecular meshwork through Rab13/PKA signalling complex |
| title_full_unstemmed | Vasoactive intestinal peptide reduces ocular hypertension by regulating tight junction of trabecular meshwork through Rab13/PKA signalling complex |
| title_short | Vasoactive intestinal peptide reduces ocular hypertension by regulating tight junction of trabecular meshwork through Rab13/PKA signalling complex |
| title_sort | vasoactive intestinal peptide reduces ocular hypertension by regulating tight junction of trabecular meshwork through rab13 pka signalling complex |
| topic | Ocular hypertension vasoactive intestinal peptide tight junction trabecular meshwork Rab13–PKA signalling complex |
| url | https://www.tandfonline.com/doi/10.1080/07853890.2025.2534527 |
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