Efectos de nuevos agentes regenerativos biomiméticos sobre la cicatrización corneal en un modelo experimental de úlceras posquirúrgicas / Effects of new biomimetic regenerating agents on corneal wound healing in an experimental model of post-surgical corneal ulcers

OBJETIVO: El propósito de este estudio es evaluar la eficacia de la aplicación tópica de RGTA-cacicol (Regenerative Agent-cacicol) en un modelo experimental de úlcera corneal tras queratectomía fotorrefractiva (PRK) en ratones. MÉTODOS: Los ratones fueron tratados mediante cirugía PRK con una zona de ablación de 2,0 mm en la córnea central y 45 μm de profundidad con un láser excimer VISX Star S2. Las córneas fueron tratadas tópicamente con gotas de cacicol una hora y 48 h después de la lesión. Los grupos control recibieron BSS (solución estéril de irrigación) en la misma posología. Los eventos clínicos e histopatológicos fueron evaluados 1, 2, 3 y 7 días después de la cirugía. Sobre secciones obtenidas a través de la región central de las córneas se realizaron técnicas inmunofluorescentes para α-SMA (transformación de miofibroblastos), E-cadherina (ensamblaje de las células epiteliales) y β-tubulina neuronal clase III (inervación). RESULTADOS: Las córneas tratadas tópicamente con cacicol durante 7 días mostraron un mayor grado de transparencia en comparación con el control. Además presentaban una mejor citoarquitectura epitelial. El análisis de los perfiles α-SMA en el estroma demostró que el cacicol reduce o retrasa la presencia de miofibroblastos en el estroma en comparación con BSS (p < 0,001). Finalmente se encontró un posible efecto neurorregenerativo de cacicol en córneas tratadas mediante una lesión experimental PRK. En algunos casos se podría dar variabilidad interindividual debido al diseño del modelo experimental, lo que supone una limitación a tener en cuenta pese a la significación estadística de los datos. CONCLUSIONES: En un modelo de lesiones quirúrgicas inducidas por láser en la córnea, la aplicación tópica de RGTA podría evitar la formación de cicatrices y la aparición de miofibroblastos y favorecer la regeneración nerviosa

OBJECTIVE: The purpose of this study is to assess the effectiveness of the topical application of cacicol regenerating agent (RGTA) in an experimental model of corneal ulcer after photorefractive keratectomy (PRK) in mice. METHODS: Mice were subjected to PRK surgery with a 2.0 mm ablation zone on the central cornea and 45 mm of depth on a VISX Star S2 excimer laser. Corneas were treated topically with cacicol drops 1 hour and 48 hours after injury. Control groups received balanced salt solution (BSS) in the same dosage. Clinical and histopathological events were evaluated at 1, 2, 3 and 7 days after surgery. Sections obtained through the central region of the corneas were used to analyze the histopathological events of injured and healed corneas. αSMA (myofibroblast transformation), E cadherin (assembly of epithelial cells) and neuronal class III β-tubulin (innervation) were performed. RESULTS: Corneas treated topically with cacicol for 7 days showed a greater degree of transparency compared to controls. cacicol treated corneas showed improved epithelial cytoarchitecture. Analysis of αSMA profiles in the stroma showed that cacicol reduced or delayed the presence of myofibroblasts in the stroma compared to BSS (P<0.001). Finally, a putative neuroregenerative effect of cacicol was found in corneas subjected to an experimental PRK lesion. In some cases some interindividual variability could be observed due to the design of the experimental model. This is a limitation to consider, despite the statistical significance of the data. CONCLUSIONS: In a model of laser induced surgical lesions in the cornea, topical application of an RGTA (i.e. cacicol) could be involved in avoiding myofibroblast scarring formation and promoting nerve regeneration

Effects of new biomimetic regenerating agents on corneal wound healing in an experimental model of post-surgical corneal ulcers.

OBJECTIVE: The purpose of this study is to assess the effectiveness of the topical application of cacicol regenerating agent (RGTA) in an experimental model of corneal ulcer after photorefractive keratectomy (PRK) in mice. METHODS: Mice were subjected to PRK surgery with a 2.0mm ablation zone on the central cornea and 45mm of depth on a VISX Star S2 excimer laser. Corneas were treated topically with cacicol drops 1hour and 48hours after injury. Control groups received balanced salt solution (BSS) in the same dosage. Clinical and histopathological events were evaluated at 1, 2, 3 and 7 days after surgery. Sections obtained through the central region of the corneas were used to analyze the histopathological events of injured and healed corneas. αSMA (myofibroblast transformation), E cadherin (assembly of epithelial cells) and neuronal class III ß-tubulin (innervation) were performed. RESULTS: Corneas treated topically with cacicol for 7 days showed a greater degree of transparency compared to controls. cacicol treated corneas showed improved epithelial cytoarchitecture. Analysis of αSMA profiles in the stroma showed that cacicol reduced or delayed the presence of myofibroblasts in the stroma compared to BSS (P<0.001). Finally, a putative neuroregenerative effect of cacicol was found in corneas subjected to an experimental PRK lesion. In some cases some interindividual variability could be observed due to the design of the experimental model. This is a limitation to consider, despite the statistical significance of the data. CONCLUSIONS: In a model of laser induced surgical lesions in the cornea, topical application of an RGTA (i.e. cacicol) could be involved in avoiding myofibroblast scarring formation and promoting nerve regeneration.