ABSTRACT
La hipoacusia afecta a más de 1.500 millones de personas mundialmente. Los principales medios de rehabilitación usados son los audífonos e implantes cocleares (IC). El IC eléctrico convierte el sonido en impulsos eléctricos que estimulan, directamente, a las neuronas del ganglio espiral para proveer sensación auditiva. Tiene como desventaja una amplia dispersión espacial de la corriente, limitando la resolución espectral y el rango dinámico de codificación sonoro, lo que conduce a una mala comprensión del habla en entornos ruidosos y mala apreciación de la música. En los últimos años se ha estudiado utilizar estimulación óptica en vez de eléctrica, pues emite estímulos con mayor selectividad espacial. Se han descrito IC ópticos usando luz infrarroja y otros con métodos de optogenética, estos últimos requieren de la expresión de proteínas fotosensibles inducidas por virus adenoasociados. Se ha visto que la selectividad espectral de la estimulación optogenética es indistinguible de la acústica, y permitió tasas de disparo casi fisiológicas con buena precisión temporal hasta 250 Hz de estimulación. Estudios que compararon un sistema de IC óptico con uno eléctrico concluyen que el uso de optogenética permitiría una restauración de la audición con una selectividad espectral mejorada en comparación con un IC eléctrico.
Hearing loss affects more than 1.5 billion people worldwide. The main means of rehabilitation used are hearing aids and cochlear implants (CI). The electrical CI converts sound into electrical impulses that directly stimulate neurons in the spiral ganglion to provide auditory sensation; it has the disadvantage of a wide spatial dispersion of the current, limiting the spectral resolution and the dynamic range of sound coding, which leads to a poor understanding of speech in noisy environments and a poor appreciation of music. In recent years, the use of optical stimulation instead of electrical stimulation have been studied since it emits stimuli with greater spatial selectivity. Optical CIs have been described using infrared light and others using optogenetic methods, the latter requiring the expression of photosensitive proteins induced by adeno-associated viruses. The spectral selectivity of optogenetic stimulation has been found to be indistinguishable from acoustic stimulation and allowed near-physiological firing rates with good temporal accuracy up to 250 Hz stimulation. Studies comparing an optical and an electrical CI system conclude that the use of optogenetics would allow hearing restoration with improved spectral selectivity compared to an electrical CI.
Subject(s)
Cochlear Implantation/methods , Optogenetics/methods , Hearing Loss/rehabilitation , Cochlear ImplantsABSTRACT
BACKGROUND: Molecular brain therapies require the development of molecular switches to control gene expression in a limited and regulated manner in time and space. Light-switchable gene systems allow precise control of gene expression with an enhanced spatio-temporal resolution compared to chemical inducers. In this work, we adapted the existing light-switchable Light-On system into a lentiviral platform, which consists of two modules: (i) one for the expression of the blue light-switchable transactivator GAVPO and (ii) a second module containing an inducible-UAS promoter (UAS) modulated by a light-activated GAVPO. RESULTS: In the HEK293-T cell line transfected with this lentiviral plasmids system, the expression of the reporter mCherry increased between 4 to 5 fold after light induction. A time expression analysis after light induction during 24 h revealed that mRNA levels continuously increased up to 9 h, while protein levels increased throughout the experiment. Finally, transduction of cultured rat hippocampal neurons with this dual Light-On lentiviral system showed that CDNF, a potential therapeutic trophic factor, was induced only in cells exposed to blue light. CONCLUSIONS: In conclusion, the optimized lentiviral platform of the Light-On system provides an efficient way to control gene expression in neurons, suggesting that this platform could potentially be used in biomedical and neuroscience research, and eventually in brain therapies for neurodegenerative diseases.