Cochlea cell-specific marker expression upon in vitro Hes1 knockdown

NOTCH pathway proteins, including the transcriptional factor HES1, play crucial roles in the development of the inner ear by means of the lateral inhibition mechanism, in which supporting cells have their phenotype preserved while they are prevented from becoming hair cells. Genetic manipulation of this pathway has been demonstrated to increase hair cell number. The present study aimed to investigate gene expression effects in hair cells and supporting cells after Hes1-shRNA lentivirus transduction in organotypic cultures of the organ of Corti from postnatal-day-3 mice. Forty-eight hours after in vitro knockdown, Hes1 gene expression was reduced at both mRNA and protein levels. Myo7a (hair cell marker) and Sox2 (progenitor cell marker) mRNA levels also significantly increased. The modulation of gene expression in the organ of Corti upon Hes1 knockdown is consistent with cell phenotypes related to lateral inhibition mechanism interference in the inner ear. The lentivirus-based expression of Hes1-shRNA is a valuable strategy for genetic interference in the organ of Corti and for future evaluation of its efficacy in protocols aiming at the regeneration of hair cells in vivo.

Influencia de las zonas cocleares muertas sobre la autopercepción de las habilidades auditivas en adultos con hipoacusia sensorioneural bilateral / Influence of cochlear dead regions on self-perception hearing abilities in adults with bilateral sensorineural hearing loss

RESUMEN Introducción: Las zonas cocleares muertas son áreas de la membrana basilar donde las células ciliadas y/o fibras del nervio auditivo no son funcionales, lo que puede alterar el análisis temporal de una señal acústica. Los efectos funcionales que podrían generar aún no son claros, y establecerlos a través del uso de cuestionarios de autopercepción, proporcionaría información de utilidad para el manejo audiológico de los pacientes. Objetivo: Determinar la relación entre la presencia de zonas cocleares muertas y la autopercepción de las habilidades auditivas en adultos con hipoacusia sensorioneural bilateral. Material y método: Se evaluaron 20 sujetos con hipoacusia bilateral simétrica, entre 51 y 75 años, sin antecedentes de uso de audífonos. Las zonas cocleares muertas fueron evaluadas mediante la prueba TEN en 1, 2, 3 y 4 kHz; y la autopercepción de habilidades auditivas fue medida en los participantes a través del cuestionario de doce preguntas, IROS12. Resultados: La presencia de zonas cocleares muertas se observó en 10 pacientes. No existiendo una diferencia significativa entre grupos, sin embargo, se observaron puntuaciones más bajas de IROS12 en sujetos con zonas cocleares muertas. Conclusiones: La percepción de dificultades auditivas de individuos que presentan una hipoacusia sensorioneural bilateral simétrica moderada, con presencia de zonas cocleares muertas, no difiere significativamente de aquellos individuos que no presentan zonas cocleares muertas.

ABSTRACT Introduction: Cochlear dead regions are areas of the basilar membrane where the hair cells and/or auditory nerve fibers are not functional, which can alter the temporal analysis of an acoustic signal. The functional effects that could generate still are not entirely clear, and set through the use of self-perception questionnaires, provide useful information for audiological management of patients. Aim: To investigate the relationship between the presence of cochlear dead regions and the self-reported of listening difficulties of adults with bilateral sensorineural hearing loss. Material and Method: Twenty adults with symmetric bilateral sensorineural hearing loss, aged 51 to 75 years were tested, without previous story of use of hearing aids. Cochlear dead regions were tested using the TEN test at 1, 2, 3 and 4 kHz. The questionnaire of twelve questions, IROS12, was applied to the participants. Results: Cochlear dead regions were present in 10 participants. No significant differences were observed between groups, however lower IROS12 scores were observed in those who had present of dead regions. Conclusion: The perception of hearing difficulties in individuals with bilateral sensorineural hearing loss with cochlear dead regions did not differ significantly from those individuals without cochlear dead regions.