Descripción del proyecto
Una visión para las personas con enfermedades oculares degenerativas
La visión nocturna de los gatos es mucho mejor que la de las personas, porque en sus ojos hay más bastones que conos. Los bastones y conos son dos tipos de fotorreceptores de la retina. Los bastones responden a la luz de bajo nivel con poca precisión espacial, pero no detectan el color. Los conos hacen lo contrario. Además, los conos modulan a los bastones ayudando a mejorar la visión diurna. Cuando se dañan los conos, los ojos tienen un problema que estos no pueden solucionar: pierden la visión clara y aguda durante el día y la capacidad de mejorarla recurriendo a la ayuda de los bastones. RODRESET está buscando nuevas formas de modular la sensibilidad de los bastones. Su éxito podría tener un impacto considerable en el tratamiento de la degeneración macular en todo el mundo.
Objetivo
In industrialized countries, age-related macular degeneration (AMD) is the leading cause of untreatable blindness. In addition to age-related disease, there are also inherited forms of macular degeneration, such as juvenile-onset Stargardt disease. These conditions, for which there are currently no effective treatments, involve the loss of photoreceptors in the central retina, where a high cone photoreceptor density is responsible for effecting high resolution vision. We recently discovered that cones can modulate the sensitivity of surrounding rod photoreceptors to enable them to be more effective in daylight conditions. In retinal disorders involving degeneration of the macular cones, this lateral interaction is impaired, leading to saturation of the rods’ dynamic range and impaired daylight vision. We have also discovered that direct modulation the neurons underlying this lateral interaction, the horizontal cells, improves quality of vision in mice lacking functional cones. Together, our results identify a specific circuitry underlying rod-mediated vision as a potential therapeutic target following macular degeneration. Here, we aim to exploit these new findings to re-establish the rods’ ability to function in daylight using two distinct approaches. Firstly, we will use direct modification of the rods to permanently shift their light sensitivity into the daylight range. A small area of modified rods that are effective in daylight, likely with a higher temporal resolution, would improve extra-foveal fixation and vision. Secondly, we intend to establish a system that confers light sensitivity onto horizontal cells, to replace light-mediated input from cones. This will restore the natural horizontal cell-derived modulation of light sensitivity to rods, allowing them to function in daylight. Thus, by utilizing our knowledge of specific aspects of retinal circuitry, we aim to develop novel therapies for improving vision in patients with advanced macular degeneration.
Ámbito científico
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Programa(s)
Régimen de financiación
ERC-ADG - Advanced GrantInstitución de acogida
WC2R 2LS London
Reino Unido