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The S1P1 receptor-selective agonist CYM-5442 protects retinal ganglion cells in endothelin-1 induced retinal ganglion cell loss

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dc.contributor.authorBlanco, Román
dc.contributor.authorMartínez Navarrete, Gema
dc.contributor.authorValiente Soriano, Francisco J.
dc.contributor.authorAvilés Trigueros, Marcelino
dc.contributor.authorPérez Rico, Consuelo
dc.contributor.authorSerrano Puebla, Ana
dc.contributor.authorBoya, Patricia
dc.contributor.authorFernández, Eduardo
dc.contributor.authorVidal Sanz, Manuel
dc.contributor.authorVilla, Pedro de la
dc.contributor.departmentOftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
dc.date.accessioned2025-03-26T13:03:00Z
dc.date.available2025-03-26T13:03:00Z
dc.date.issued2017-08-04
dc.description© 2017 Elsevier Ltd. This document is the Published Manuscript, version of a Published Work that appeared in final form in Experimental Eye Research. To access the final edited and published work see https://doi.org/10.1016/j.exer.2017.08.005es
dc.description.abstractWe investigated the feasibility and efficacy of using a specific sphingosine 1–phosphate (S1P1) receptor agonist, CYM-5442, to slow or block retinal ganglion cell (RGC) loss in endothelin-1 (ET-1) induced RGC loss. A single intravitreal injection of ET-1 (20pmol/ul), a potent vasoactive peptide that produces retinal vessels vasoconstriction, was used to induce and characterize RGC-specific cell death. CYM-5442 (1 mgr/kg) or vehicle was administered intraperitoneally for five consecutive days after ET-1-induced RGC loss. The functional extent of RGC loss injury was evaluated with pattern visual evoked potentials (VEP) and electroretinography. RGCs and retinal nerve fiber layer (RNFL) thickness were assessed in vivo using optical coherence tomography and ex vivo using Brn3a immunohistochemistry in flat-mounted retinas. ET-1 caused significant RGC loss and function loss one week after intravitreal injection. VEP showed preserved visual function after CYM-5442 administration compared to vehicle-treated animals (11.95 ± 0.86 μV vs 3.47 ± 1.20 μV, n = 12) (p < 0.05). RNFL was significantly thicker in the CYM treated-animals compared to the vehicle (93.62 ± 3.22 μm vs 77.72 ± 0.35 μm, n = 12) (p < 0.05). Furthermore, Brn3a immunohistochemistry validated this observation, showing significantly higher RGCs numbers in CYM treated rats than in the vehicle group (76,540 ± 303 vs 52,426 ± 1,932 cells/retina, n = 9) (p = 0.05). CYM-5442 administration was associated with significant retinal cleaved caspase-3 deactivation, indicating reduced apoptotic levels. The results of the present study further demonstrate the important role of S1P1 receptor agonists to lessen intravitreal ET-1 induced RGC loss.es
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dc.identifier.citationExperimental Eye Research, 2017, Vol. 164, pp. 37-45
dc.identifier.doihttps://doi.org/10.1016/j.exer.2017.08.005
dc.identifier.issnPrint: 0014-4835
dc.identifier.urihttp://hdl.handle.net/10201/152181
dc.languageenges
dc.publisherElsevieres
dc.relationThis study was supported by Fundación Séneca, Agencia de Ciencia y Tecnología Región de Murcia (19881/GERM/15), the Spanish Ministry of Economy and Competitiveness (SAF2015-67643-P, CIBER-BBN) and Instituto de Salud Carlos III (RD16/0008/0026, RD16/0008/0020).es
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S0014483517302853es
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectS1P1 receptor agonistses
dc.subjectCYM 5442es
dc.subjectRetinal ganglion cellses
dc.subjectNeuroprotectiones
dc.titleThe S1P1 receptor-selective agonist CYM-5442 protects retinal ganglion cells in endothelin-1 induced retinal ganglion cell losses
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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