<p>Optogenetics enable the restoration of light sensitivity in various retinal cell types. In degenerated retinas, dormant cones whose cell bodies are intact but no longer respond to light can be optogenetically reactivated. This restores all cone-dependent signalling pathways. In RP mouse models the hyperpolarizing opsins eNpHR and Jaws led to the optogenetic reactivation of dormant photoreceptors, with measurable light responses. This was accompanied by improvements in behavioral tests. The transplantation of optogenetically modified photoreceptors also shows functional integration into the retina. Near infrared-based optogenetic approaches enable the activation of optogenetic tools while simultaneously preserving the remaining natural vision in patients with intact photoreceptors and residual visual function, without causing phototoxic effects. The translation from mouse to human models, however, requires further optimization to maximize the therapeutic efficiency. Stimulation goggles represent a&#xa0;potential approach for the everyday application of optogenetic tools and could be enhanced with artificial intelligence-assisted image processing to improve resolution and adaptability. Overall, the combination of optogenetics, cell therapy and innovative stimulation strategies provides a&#xa0;promising approach to restoring vision in retinal degenerative diseases.</p>

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Optogenetische Reaktivierung dormanter Zapfenphotorezeptoren

  • Gabriela Guzman,
  • Jasmin Zorn,
  • Sarah Kunze,
  • Volker Busskamp

摘要

Optogenetics enable the restoration of light sensitivity in various retinal cell types. In degenerated retinas, dormant cones whose cell bodies are intact but no longer respond to light can be optogenetically reactivated. This restores all cone-dependent signalling pathways. In RP mouse models the hyperpolarizing opsins eNpHR and Jaws led to the optogenetic reactivation of dormant photoreceptors, with measurable light responses. This was accompanied by improvements in behavioral tests. The transplantation of optogenetically modified photoreceptors also shows functional integration into the retina. Near infrared-based optogenetic approaches enable the activation of optogenetic tools while simultaneously preserving the remaining natural vision in patients with intact photoreceptors and residual visual function, without causing phototoxic effects. The translation from mouse to human models, however, requires further optimization to maximize the therapeutic efficiency. Stimulation goggles represent a potential approach for the everyday application of optogenetic tools and could be enhanced with artificial intelligence-assisted image processing to improve resolution and adaptability. Overall, the combination of optogenetics, cell therapy and innovative stimulation strategies provides a promising approach to restoring vision in retinal degenerative diseases.