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• W4309226112 abstract "Abstract Retinal dystrophies of genetic origin are often associated with mutations in the genes involved in the phototransduction cascade in photoreceptors, a paradigmatic signaling pathway mediated by G protein-coupled receptors. Photoreceptor viability is strictly dependent on the levels of the second messengers cGMP and Ca 2+ . Here we explored the possibility of modulating the phototransduction cascade in mouse rods using direct or liposome-mediated administration of a recombinant protein crucial for regulating the interplay of the second messengers in photoreceptor outer segments. The effects of administration of the free and liposome-encapsulated human guanylate cyclase-activating protein (GCAP1) were compared in biological systems of increasing complexity ( in cyto, ex vivo , and in vivo). Analysis of protein biodistribution and direct measurement of functional alteration in rod photoresponses show that the exogenous GCAP1 protein is fully incorporated into the mouse retina and photoreceptor outer segments. Furthermore, only in the presence of a point mutation associated with cone-rod dystrophy in humans p.(E111V), protein delivery induces a disease-like electrophysiological phenotype, consistent with constitutive activation of the retinal guanylate cyclase. Our study demonstrates that both direct and liposome-mediated protein delivery are powerful tools for targeting signaling cascades in neuronal cells, which could be particularly important for the treatment of autosomal dominant genetic diseases." @default.
• W4309226112 created "2022-11-24" @default.
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• W4309226112 date "2022-11-13" @default.
• W4309226112 modified "2023-09-27" @default.
• W4309226112 title "Recombinant protein delivery enables modulation of the phototransduction cascade in mouse retina" @default.
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• W4309226112 doi "https://doi.org/10.1101/2022.11.10.516027" @default.
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