Cilastatin as a Potential Anti-Inflammatory and Neuroprotective Treatment in the Management of Glaucoma
Glaucoma is a neurodegenerative disease that causes blindness. In this study, we aimed to evaluate the protective role of cilastatin (CIL), generally used in the treatment of nephropathologies associated with inflammation, in an experimental mouse model based on unilateral (left) laser-induced ocula...
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MDPI AG
2024-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/6/3115 |
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| author | Miguel A. Martínez-López Sara Rubio-Casado Diego San Felipe Beatriz Martín-Sánchez José A. Fernández-Albarral Elena Salobrar-García José A. Matamoros José M. Ramírez Rosa de Hoz Juan J. Salazar Eva M. Marco Ana I. Ramírez Alberto Lázaro Meritxell López-Gallardo |
| author_facet | Miguel A. Martínez-López Sara Rubio-Casado Diego San Felipe Beatriz Martín-Sánchez José A. Fernández-Albarral Elena Salobrar-García José A. Matamoros José M. Ramírez Rosa de Hoz Juan J. Salazar Eva M. Marco Ana I. Ramírez Alberto Lázaro Meritxell López-Gallardo |
| author_sort | Miguel A. Martínez-López |
| collection | DOAJ |
| description | Glaucoma is a neurodegenerative disease that causes blindness. In this study, we aimed to evaluate the protective role of cilastatin (CIL), generally used in the treatment of nephropathologies associated with inflammation, in an experimental mouse model based on unilateral (left) laser-induced ocular hypertension (OHT). Male Swiss mice were administered CIL daily (300 mg/kg, i.p.) two days before OHT surgery until sacrifice 3 or 7 days later. Intraocular Pressure (IOP), as well as retinal ganglion cell (RGC) survival, was registered, and the inflammatory responses of macroglial and microglial cells were studied via immunohistochemical techniques. Results from OHT eyes were compared to normotensive contralateral (CONTRA) and naïve control eyes considering nine retinal areas and all retinal layers. OHT successfully increased IOP values in OHT eyes but not in CONTRA eyes; CIL did not affect IOP values. Surgery induced a higher loss of RGCs in OHT eyes than in CONTRA eyes, while CIL attenuated this loss. Similarly, surgery increased macroglial and microglial activation in OHT eyes and to a lesser extent in CONTRA eyes; CIL prevented both macroglial and microglial activation in OHT and CONTRA eyes. Therefore, CIL arises as a potential effective strategy to reduce OHT-associated damage in the retina of experimental mice. |
| first_indexed | 2024-04-24T18:12:12Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T18:12:12Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3d67b18f79b8456a8341e9351e261e322024-03-27T13:45:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-03-01256311510.3390/ijms25063115Cilastatin as a Potential Anti-Inflammatory and Neuroprotective Treatment in the Management of GlaucomaMiguel A. Martínez-López0Sara Rubio-Casado1Diego San Felipe2Beatriz Martín-Sánchez3José A. Fernández-Albarral4Elena Salobrar-García5José A. Matamoros6José M. Ramírez7Rosa de Hoz8Juan J. Salazar9Eva M. Marco10Ana I. Ramírez11Alberto Lázaro12Meritxell López-Gallardo13Department of Immunology, Ophthalmology and ORL, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, SpainDepartment of Physiology, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, SpainDepartment of Physiology, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, SpainDepartment of Physiology, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, SpainInstitute of Ophthalmologic Research Ramón Castroviejo, Universidad Complutense de Madrid, 28040 Madrid, SpainInstitute of Ophthalmologic Research Ramón Castroviejo, Universidad Complutense de Madrid, 28040 Madrid, SpainInstitute of Ophthalmologic Research Ramón Castroviejo, Universidad Complutense de Madrid, 28040 Madrid, SpainDepartment of Immunology, Ophthalmology and ORL, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, SpainInstitute of Ophthalmologic Research Ramón Castroviejo, Universidad Complutense de Madrid, 28040 Madrid, SpainInstitute of Ophthalmologic Research Ramón Castroviejo, Universidad Complutense de Madrid, 28040 Madrid, SpainInstitute of Ophthalmologic Research Ramón Castroviejo, Universidad Complutense de Madrid, 28040 Madrid, SpainInstitute of Ophthalmologic Research Ramón Castroviejo, Universidad Complutense de Madrid, 28040 Madrid, SpainDepartment of Physiology, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, SpainDepartment of Physiology, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, SpainGlaucoma is a neurodegenerative disease that causes blindness. In this study, we aimed to evaluate the protective role of cilastatin (CIL), generally used in the treatment of nephropathologies associated with inflammation, in an experimental mouse model based on unilateral (left) laser-induced ocular hypertension (OHT). Male Swiss mice were administered CIL daily (300 mg/kg, i.p.) two days before OHT surgery until sacrifice 3 or 7 days later. Intraocular Pressure (IOP), as well as retinal ganglion cell (RGC) survival, was registered, and the inflammatory responses of macroglial and microglial cells were studied via immunohistochemical techniques. Results from OHT eyes were compared to normotensive contralateral (CONTRA) and naïve control eyes considering nine retinal areas and all retinal layers. OHT successfully increased IOP values in OHT eyes but not in CONTRA eyes; CIL did not affect IOP values. Surgery induced a higher loss of RGCs in OHT eyes than in CONTRA eyes, while CIL attenuated this loss. Similarly, surgery increased macroglial and microglial activation in OHT eyes and to a lesser extent in CONTRA eyes; CIL prevented both macroglial and microglial activation in OHT and CONTRA eyes. Therefore, CIL arises as a potential effective strategy to reduce OHT-associated damage in the retina of experimental mice.https://www.mdpi.com/1422-0067/25/6/3115retinaglaucomaocular hypertension (OHT)retinal ganglion cells (RGCs)macroglial cellsmicroglial cells |
| spellingShingle | Miguel A. Martínez-López Sara Rubio-Casado Diego San Felipe Beatriz Martín-Sánchez José A. Fernández-Albarral Elena Salobrar-García José A. Matamoros José M. Ramírez Rosa de Hoz Juan J. Salazar Eva M. Marco Ana I. Ramírez Alberto Lázaro Meritxell López-Gallardo Cilastatin as a Potential Anti-Inflammatory and Neuroprotective Treatment in the Management of Glaucoma International Journal of Molecular Sciences retina glaucoma ocular hypertension (OHT) retinal ganglion cells (RGCs) macroglial cells microglial cells |
| title | Cilastatin as a Potential Anti-Inflammatory and Neuroprotective Treatment in the Management of Glaucoma |
| title_full | Cilastatin as a Potential Anti-Inflammatory and Neuroprotective Treatment in the Management of Glaucoma |
| title_fullStr | Cilastatin as a Potential Anti-Inflammatory and Neuroprotective Treatment in the Management of Glaucoma |
| title_full_unstemmed | Cilastatin as a Potential Anti-Inflammatory and Neuroprotective Treatment in the Management of Glaucoma |
| title_short | Cilastatin as a Potential Anti-Inflammatory and Neuroprotective Treatment in the Management of Glaucoma |
| title_sort | cilastatin as a potential anti inflammatory and neuroprotective treatment in the management of glaucoma |
| topic | retina glaucoma ocular hypertension (OHT) retinal ganglion cells (RGCs) macroglial cells microglial cells |
| url | https://www.mdpi.com/1422-0067/25/6/3115 |
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