Objectif The death and dysfunction of retinal ganglion cells (RGC) is a major cause of blindness in traumatic and degenerative ocular disease. For example, 60M people are affected by glaucoma with 4.5M becoming blind in both eyes, whilst optic neuritis affects 5/100,000 people and represents a significant problem for sufferers. RGC are the sole projection neurons and their axons make up the optic nerve, making them exquisitely sensitive to injury. As CNS neurons are irreplaceable, neuroprotective strategies are paramount to therapies aimed at preserving vision but as of yet, no such therapy exists. Current research has demonstrated significant neuroprotection by mesenchymal stem cells (MSC) including those from the bone marrow (BMSC), acting not as replacements for RGC but rather, as paracrine-mediated support cells. Clinical trials are already ongoing to test their efficacy in patients. Despite this, the exact mechanism behind their neuroprotective potential is not well understood. Recent studies have shown that exosomes, extracellular vesicles containing proteins, mRNA and miRNA may mediate much of the paracrine support offered by MSC and thus act as an easily purifiable cell-free alternative therapy for RGC neuroprotection. This proposal aims to assess the therapeutic efficacy of BMSC-derived exosomes, their characterisation and that of their RNA cargo. We will test these exosomes in animal models of traumatic (optic nerve crush) and degenerative (glaucoma) eye disease. Specifically, this proposal employs a novel strategy to promote RGC survival (relevant to ONC and glaucoma) and axon regeneration (relevant to optic nerve crush) through the use of exosomal delivery of mRNA/miRNA into injured RGC utilizing in vitro and in vivo injury models, RNAseq and CRISPR technology. Champ scientifique sciences naturellessciences biologiquesneurobiologiesciences médicales et de la santémédecine cliniqueophtalmologieglaucomesciences naturellessciences biologiquesbiologie cellulairesciences médicales et de la santébiotechnologie médicaletechnologies cellulairescellule souchesciences naturellessciences biologiquesgénétiqueARN Mots‑clés Neuroprotection retinal neurons optic nerve regeneration glaucoma mesenchymal stem cells Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Thème(s) MSCA-IF-2016 - Individual Fellowships Appel à propositions H2020-MSCA-IF-2016 Voir d’autres projets de cet appel Régime de financement MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinateur THE UNIVERSITY OF BIRMINGHAM Contribution nette de l'UE € 269 857,80 Adresse Edgbaston B15 2TT Birmingham Royaume-Uni Voir sur la carte Région West Midlands (England) West Midlands Birmingham Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Autres sources de financement € 0,00 Partenaires (1) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire Partenaire Les organisations partenaires contribuent à la mise en œuvre de l’action, mais ne signent pas la convention de subvention. United States Department of Health and Human Services États-Unis Contribution nette de l'UE € 0,00 Adresse Independence avenue s. w. 200 20201 Washington d.c. Voir sur la carte Type d’activité Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments) Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Autres sources de financement € 172 130,40
