Martínez López, Miguel ÁngelRubio Casado, SaraSan Felipe Riba, DiegoMartín Sánchez, BeatrizFernández Albarral, JoséGarcía Martín, Elena SalobrarMatamoros, José AntonioRamírez Sebastián, José ManuelHoz Montañana, María Rosa DeSalazar Corral, Juan JoséMarco López, Eva MaríaLázaro Fernández, AlbertoLópez Gallardo, MeritxellRamírez Sebastián, Ana Isabel2024-03-122024-03-122024-03-07Martínez-López, M.A.; Rubio-Casado, S.; San Felipe, D.; Martín-Sánchez, B.; Fernández-Albarral, J.A.; Salobrar-García, E.; Matamoros, J.A.; Ramírez, J.M.; de Hoz, R.; Salazar, J.J.; et al. Cilastatin as a Potential Anti-Inflammatory and Neuroprotective Treatment in the Management of Glaucoma. Int. J. Mol. Sci. 2024, 25, 3115. https://doi.org/10.3390/ijms2506311510.3390/ijms25063115https://hdl.handle.net/20.500.14352/102168Submission received: 10 January 2024 / Revised: 26 February 2024 / Accepted: 5 March 2024 / Published: 7 March 2024 (This article belongs to the Special Issue Advanced Research in Retina 2.0)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.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal articlehttps://doi.org/10.3390/ijms25063115https://www.mdpi.com/1422-0067/25/6/3115#open access617.7-007.681616.8-002611.8.018.24RetinaGlaucomaOcular hypertension (OHT)Retinal ganglion cells (RGCs)Macroglial cellsMicroglial cellsNeuroinflammationCilastatinTherapeutic approachNeuroprotectionOftalmologíaMedicamentosBiología celular (Biología)3201.09 Oftalmología3208 Farmacodinámica2407 Biología Celular