Neuroprotective and intraocular pressure lowering effects of dual-functional memantine nitrate MN-08 on the experimental models of glaucoma
Abstract Glaucoma stands out as the primary cause of permanent blindness worldwide, marked by elevated intraocular pressure (IOP) and the deterioration of retinal ganglion cells (RGCs) within the optic nerve. This study aimed to investigate the therapeutic efficacy of MN-08, a novel memantine nitrat...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-06832-x |
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| author | Huihui Hu Liangmiao Wu Xiaodie Hu Minghua Wang Yewei Sun Gaoxiao Zhang Yuqiang Wang Peng Yi Zaijun Zhang |
| author_facet | Huihui Hu Liangmiao Wu Xiaodie Hu Minghua Wang Yewei Sun Gaoxiao Zhang Yuqiang Wang Peng Yi Zaijun Zhang |
| author_sort | Huihui Hu |
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| description | Abstract Glaucoma stands out as the primary cause of permanent blindness worldwide, marked by elevated intraocular pressure (IOP) and the deterioration of retinal ganglion cells (RGCs) within the optic nerve. This study aimed to investigate the therapeutic efficacy of MN-08, a novel memantine nitrate derivative, in experimental models of glaucoma. In the rat model of retinal ischemia–reperfusion injury, MN-08 prevented the reduction in retinal ganglion cell complex (GCC) thickness and RGC loss. Meanwhile, MN-08 reduced the protein levels of cleaved-caspase-3, caspase-3, and Bax, while increasing the expression of Bcl-2 compared to the model group, indicating that MN-08 exerts an inhibitory effect on the apoptosis of RGCs. Furthermore, MN-08 lowered IOP in the transient ocular hypertension and glaucoma rabbit models. MN-08 significantly increased cGMP levels in human trabecular meshwork cells (HTMCs). Elevation of cGMP induced by MN-08 was eliminated by ODQ. Moreover, MN-08 attenuated the protein levels of MLCK and p-MLC-2 in HTMCs induced by endothelin-1. Additionally, MN-08 exhibited favorable distribution profiles and pharmacokinetic parameters in normal rabbit ocular tissues following topical instillation. These findings indicate that MN-08 could antagonize NMDA receptors to protect RGCs and release NO to relax TM for the treatment of glaucoma. |
| format | Article |
| id | doaj-art-db9a5e8425e64619962a874c792e18f0 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-db9a5e8425e64619962a874c792e18f02025-08-20T03:37:27ZengNature PortfolioScientific Reports2045-23222025-07-0115111110.1038/s41598-025-06832-xNeuroprotective and intraocular pressure lowering effects of dual-functional memantine nitrate MN-08 on the experimental models of glaucomaHuihui Hu0Liangmiao Wu1Xiaodie Hu2Minghua Wang3Yewei Sun4Gaoxiao Zhang5Yuqiang Wang6Peng Yi7Zaijun Zhang8Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University and Institute of New Drug Research, Jinan University College of PharmacyDepartment of Intensive Care Unit, The First Affiliated Hospital of Jinan University and Institute of New Drug Research, Jinan University College of PharmacyState Key Laboratory of Bioactive Molecules and Druggability Assessment, and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-Cerebrovascular Diseases, and Institute of New Drug Research, Jinan UniversityDepartment of Neurology, Daqing People’s HospitalState Key Laboratory of Bioactive Molecules and Druggability Assessment, and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-Cerebrovascular Diseases, and Institute of New Drug Research, Jinan UniversityState Key Laboratory of Bioactive Molecules and Druggability Assessment, and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-Cerebrovascular Diseases, and Institute of New Drug Research, Jinan UniversityState Key Laboratory of Bioactive Molecules and Druggability Assessment, and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-Cerebrovascular Diseases, and Institute of New Drug Research, Jinan UniversityState Key Laboratory of Bioactive Molecules and Druggability Assessment, and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-Cerebrovascular Diseases, and Institute of New Drug Research, Jinan UniversityState Key Laboratory of Bioactive Molecules and Druggability Assessment, and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-Cerebrovascular Diseases, and Institute of New Drug Research, Jinan UniversityAbstract Glaucoma stands out as the primary cause of permanent blindness worldwide, marked by elevated intraocular pressure (IOP) and the deterioration of retinal ganglion cells (RGCs) within the optic nerve. This study aimed to investigate the therapeutic efficacy of MN-08, a novel memantine nitrate derivative, in experimental models of glaucoma. In the rat model of retinal ischemia–reperfusion injury, MN-08 prevented the reduction in retinal ganglion cell complex (GCC) thickness and RGC loss. Meanwhile, MN-08 reduced the protein levels of cleaved-caspase-3, caspase-3, and Bax, while increasing the expression of Bcl-2 compared to the model group, indicating that MN-08 exerts an inhibitory effect on the apoptosis of RGCs. Furthermore, MN-08 lowered IOP in the transient ocular hypertension and glaucoma rabbit models. MN-08 significantly increased cGMP levels in human trabecular meshwork cells (HTMCs). Elevation of cGMP induced by MN-08 was eliminated by ODQ. Moreover, MN-08 attenuated the protein levels of MLCK and p-MLC-2 in HTMCs induced by endothelin-1. Additionally, MN-08 exhibited favorable distribution profiles and pharmacokinetic parameters in normal rabbit ocular tissues following topical instillation. These findings indicate that MN-08 could antagonize NMDA receptors to protect RGCs and release NO to relax TM for the treatment of glaucoma.https://doi.org/10.1038/s41598-025-06832-xGlaucomaMemantine nitrateIntraocular pressureNitric oxide |
| spellingShingle | Huihui Hu Liangmiao Wu Xiaodie Hu Minghua Wang Yewei Sun Gaoxiao Zhang Yuqiang Wang Peng Yi Zaijun Zhang Neuroprotective and intraocular pressure lowering effects of dual-functional memantine nitrate MN-08 on the experimental models of glaucoma Scientific Reports Glaucoma Memantine nitrate Intraocular pressure Nitric oxide |
| title | Neuroprotective and intraocular pressure lowering effects of dual-functional memantine nitrate MN-08 on the experimental models of glaucoma |
| title_full | Neuroprotective and intraocular pressure lowering effects of dual-functional memantine nitrate MN-08 on the experimental models of glaucoma |
| title_fullStr | Neuroprotective and intraocular pressure lowering effects of dual-functional memantine nitrate MN-08 on the experimental models of glaucoma |
| title_full_unstemmed | Neuroprotective and intraocular pressure lowering effects of dual-functional memantine nitrate MN-08 on the experimental models of glaucoma |
| title_short | Neuroprotective and intraocular pressure lowering effects of dual-functional memantine nitrate MN-08 on the experimental models of glaucoma |
| title_sort | neuroprotective and intraocular pressure lowering effects of dual functional memantine nitrate mn 08 on the experimental models of glaucoma |
| topic | Glaucoma Memantine nitrate Intraocular pressure Nitric oxide |
| url | https://doi.org/10.1038/s41598-025-06832-x |
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