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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Detalles Bibliográficos
Autores: Martínez López, Miguel Ángel, Rubio Casado, Sara, San Felipe Riba, Diego, Martín Sánchez, Beatriz, Fernández Albarral, José, García Martín, Elena Salobrar, Matamoros, José Antonio, Ramírez Sebastián, José Manuel, Hoz Montañana, María Rosa De, Salazar Corral, Juan José, Marco López, Eva María, Lázaro Fernández, Alberto, López Gallardo, Meritxell, Ramírez Sebastián, Ana Isabel
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/102168
Acceso en línea:https://hdl.handle.net/20.500.14352/102168
Access Level:acceso abierto
Palabra clave:617.7-007.681
616.8-002
611.8.018.24
Retina
Glaucoma
Ocular hypertension (OHT)
Retinal ganglion cells (RGCs)
Macroglial cells
Microglial cells
Neuroinflammation
Cilastatin
Therapeutic approach
Neuroprotection
Oftalmología
Medicamentos
Biología celular (Biología)
3201.09 Oftalmología
3208 Farmacodinámica
2407 Biología Celular
Descripción
Sumario: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.

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