Carlos Daniel Díaz-Palomera’s research while affiliated with Centro Universitario de Ciencias de la Salud and other places

Corneal chemical burns (CCBs) frequently result in corneal fibrosis or haze, an opacity of the cornea that obstructs vision and induces corneal blindness. Diverse strategies have been employed to prevent or reduce CCB-related corneal haze. In this study, we evaluated the physicochemical characteristics and biologic effects of a topical pirfenidone (PFD)-loaded liposomal formulation (PL) on a corneal alkali burn mice model. We found that PL was appropriate for ocular application due to its physiologic tear pH, osmolarity and viscosity suitable for topical ophthalmic use. Regarding its therapeutic activity, PL-treated mice had significantly reduced haze size and density, corneal edema, corneal thickness, and corneal inflammatory infiltration, in contrast to PFD in aqueous solution (p < 0.01). Importantly, the antifibrotic activity of PL (reduction of corneal haze) was associated with modulation of transforming growth factor (TGF)-β and Interleukin (IL)-1β genes. PL suppressed TGF-β expression and restored normal IL-1β expression in corneal tissue more efficiently in contrast to PFD in aqueous solution. In conclusion, PFD showed essential anti-inflammatory and anti-fibrotic effects in the treatment of alkali burns. Noteworthy, a new formulation of PFD-loaded liposomes remarkably improved these effects, standing out as a promising treatment for corneal haze.

Introducción: La degeneración macular relacionada con la edad (DMRE) exudativa está asociada con la expresión del factor de crecimiento vascular endotelial (VEGF). Varios polimorfismos de un solo nucleótido (SNP) en el gen VEGF están asociados con diferentes patrones de expresión de esta citocina (polimorfismos funcionales). En este estudio consideramos 4 SNP que están ubicados en la región promotora (rs699947 A/C, rs833061 C/T, rs1005230 C/T y rs1570360 A/G) y dos en la región 5’ no traducida (rs2010963 C/G y rs25648 C/T) que tienen efecto sobre la regulación de la transcripción. Objetivo: Asociar SNP funcionales con la DMRE exudativa en población mexicana. Métodos: A través de reacción en cadena de la polimerasa con ensayos de discriminación alélica con sondas Taqman®, los polimorfismos fueron genotipados. Las frecuencias genotípicas se compararon utilizando todos los modelos de herencia. Resultados: Los SNP fueron genotipados en 105 pacientes diagnosticados con DMRE exudativa (61 mujeres y 44 hombres, edad promedio 74.28 ± 8.32 años) y en 102 sujetos control sanos (61 mujeres y 41 hombres, edad promedio 67.41 ± 5.78 años). Los genotipos en ambos grupos estaban en el equilibrio de Hardy-Weinberg. En cualquiera de los SNP analizados, la frecuencia de alelos menores fue diferente entre los grupos, con significación estadística. Los genotipos no mostraron diferencias estadísticamente significativas entre la DMRE exudativa y los grupos control (p > 0.05). Conclusión: No se encontró asociación entre los SNP estudiados y la presencia de DMRE exudativa en la población mexicana analizada. Consideramos necesario un análisis adicional en muestras más grandes para confirmar estos hallazgos.

Introduction: Various pro-inflammatory cytokines and growth factors have been implicated in the pathogenesis of pterygium (Pt); however, the effect of cytokines produced by helper T lymphocytes (Th) has been poorly studied. To date, only interleukin 4 (IL-4) from Th lymphocytes has been linked to Pt recurrence. Therefore, this study aimed to evaluate the expression of Th cytokines and Th transcription factors in primary Pt. Methods: Pt biopsies were obtained from 28 eyes of 28 Mexican patients undergoing primary excision of Pt with conjunctival autograft. Conjunctival biopsies of 8 patients undergoing cataract surgery were used as the control group. Gene expression of Th cytokines - interferon gamma (IFN-γ), IL-13, IL-17, IL-10-, as well as gene expression of Th transcription factors T-bet, GATA3, Foxp3 and RORγt, was analyzed by real-time RT-PCR. results: We found decreased expression of markers T-bet, GATA3, RORγt, IFN- γ, IL-13 and IL-10 in Pt. We found a sixfold increase in the expression of IL-17 and Foxp3 in Pt compared to healthy conjunctiva (p < 0.0001); this increase was dependent on Pt size. Conclusions: The increased expression of IL-17 and Foxp3 in Pt samples suggests the presence of IL-17+ Foxp3⁺ Th lymphocytes, a subset of the Th population with the ability to suppress T cell proliferation and promote tumor progression. Therefore, IL17⁺ Foxp3⁺ Th cells may be involved in the occurrence and growth of Pt.