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15 results on '"Toualbi, Lyes"'

7. Control of Microbial Opsin Expression in Stem Cell Derived Cones for Improved Outcomes in Cell Therapy

Author

Garita-Hernandez, Marcela, primary, Chaffiol, Antoine, additional, Guibbal, Laure, additional, Routet, Fiona, additional, Khabou, Hanen, additional, Riancho, Luisa, additional, Toualbi, Lyes, additional, Picaud, Serge, additional, Sahel, José-Alain, additional, Goureau, Olivier, additional, Duebel, Jens, additional, and Dalkara, Deniz, additional

Published
2021
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13. Optogenetic Light Sensors in Human Retinal Organoids

Author

Garita-Hernandez, Marcela, Guibbal, Laure, Toualbi, Lyes, Routet, Fiona, Chaffiol, Antoine, Winckler, Céline, Harinquet, Marylin, Robert, Camille, Fouquet, Stéphane, Bellow, Sébastien, Sahel, José-Alain, Goureau, Olivier, Duebel, Jens, Dalkara, Deniz, Institut de la Vision, and Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
optogenes, retinal organoids, trafficking, [SDV]Life Sciences [q-bio], ER stress, hiPSC, localization, Neuroscience, Original Research
Abstract

International audience; Optogenetic technologies paved the way to dissect complex neural circuits and monitor neural activity using light in animals. In retinal disease, optogenetics has been used as a therapeutic modality to reanimate the retina after the loss of photoreceptor outer segments. However, it is not clear today which ones of the great diversity of microbial opsins are best suited for therapeutic applications in human retinas as cell lines, primary cell cultures and animal models do not predict expression patterns of microbial opsins in human retinal cells. Therefore, we sought to generate retinal organoids derived from human induced pluripotent stem cells (hiPSCs) as a screening tool to explore the membrane trafficking efficacy of some recently described microbial opsins. We tested both depolarizing and hyperpolarizing microbial opsins including CatCh, ChrimsonR, ReaChR, eNpHR 3.0, and Jaws. The membrane localization of eNpHR 3.0, ReaChR, and Jaws was the highest, likely due to their additional endoplasmic reticulum (ER) release and membrane trafficking signals. In the case of opsins that were not engineered to improve trafficking efficiency in mammalian cells such as CatCh and ChrimsonR, membrane localization was less efficient. Protein accumulation in organelles such as ER and Golgi was observed at high doses with CatCh and ER retention lead to an unfolded protein response. Also, cytoplasmic localization was observed at high doses of ChrimsonR. Our results collectively suggest that retinal organoids derived from hiPSCs can be used to predict the subcellular fate of optogenetic proteins in a human retinal context. Such organoids are also versatile tools to validate other gene therapy products and drug molecules.

Published
2018
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14. Choc toxique staphylococcique menstruel : à propos d'un cas.

Author

Leseigneur, Florian, Toualbi, Lyes, Rieutord, André, Chaumais, Marie-Camille, and Rouard, Caroline

Abstract

Menstrual toxic shock syndrome (mTSS) is a rare but serious disease with multiorgan failure. It occurs mainly in young women using super-absorbent tampon material. The present article documents the case of a young 19-year-old woman, with no history, having developed a mTSS after tampon use. Laboratory investigations revealed a toxigenic strain of Staphylococcus aureus producing toxic shock syndrome toxin (TSST-1). Resuscitative mesures and appropriate antibiotic therapy led to favorable outcome despite cardiac complications after administration of vasopressors. Nowadays, the patient's recovery is complete. Providing the good use of gynecology medical devices, especially in high-risk patients participate in disease prevention to limit the development of mTSS associated with complications and death. These widely used manufacturing products are not without risk. Among healthcare professionals involved in these patients' management, pharmacists could have a major place in the counseling about menstrual material, absorbency rating and risk connected with an extended wear and as well as referring patients for urgent management in case of suspicion of mTSS. [ABSTRACT FROM AUTHOR]

Published
2017
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15. Successful large gene augmentation of USH2Awith non-viral episomal vectors

Author

Toms, Maria, Toualbi, Lyes, Almeida, Patrick V., Harbottle, Richard, and Moosajee, Mariya

Abstract

USH2Amutations are a common cause of autosomal recessive retinitis pigmentosa (RP) and Usher syndrome, for which there are currently no approved treatments. Gene augmentation is a valuable therapeutic strategy for treating many inherited retinal diseases, however conventional adeno-associated virus (AAV) gene therapy cannot accommodate cDNAs exceeding 4.7kb, such as the 15.6kb-long USH2Acoding sequence. In the present study, we adopted an alternative strategy to successfully generate scaffold/matrix attachment region (S/MAR) DNA plasmid vectors containing the full-length human USH2Acoding sequence, a GFP reporter gene and a ubiquitous promoter (CMV or CAG), reaching a size of approximately 23kb. We assessed the vectors in transfected HEK-293 cells and USH2Apatient-derived dermal fibroblasts, in addition to ush2au507zebrafish microinjected with the vector at the one-cell stage. pS/MAR-USH2A vectors drove persistent transgene expression in patient fibroblasts with restoration of usherin. Twelve months of GFP expression was detected in the photoreceptor cells, with rescue of Usher 2 complex localisation in the photoreceptors of ush2au507zebrafish retina injected with pS/MAR-USH2A. To our knowledge, this is the first reported vector which can be used to express full-length usherin with functional rescue. S/MAR DNA vectors have shown promise as a novel non-viral retinal gene therapy, warranting further translational development.

Published
2023
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