Objetivo 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. Ámbito científico ciencias naturalesciencias biológicasneurobiologíaciencias médicas y de la saludmedicina clínicaoftalmologíaglaucomaciencias naturalesciencias biológicasbiología celularciencias médicas y de la saludbiotecnología médicatecnologías celularescélulas madreciencias naturalesciencias biológicasgenéticaARN Palabras clave Neuroprotection retinal neurons optic nerve regeneration glaucoma mesenchymal stem cells Programa(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 Tema(s) MSCA-IF-2016 - Individual Fellowships Convocatoria de propuestas H2020-MSCA-IF-2016 Consulte otros proyectos de esta convocatoria Régimen de financiación MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinador THE UNIVERSITY OF BIRMINGHAM Aportación neta de la UEn € 269 857,80 Dirección Edgbaston B15 2TT Birmingham Reino Unido Ver en el mapa Región West Midlands (England) West Midlands Birmingham Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Otras fuentes de financiación € 0,00 Socios (1) Ordenar alfabéticamente Ordenar por aportación neta de la UE Ampliar todo Contraer todo Socio Las organizaciones asociadas contribuyen a la aplicación de la acción, pero no firman el acuerdo de subvención. United States Department of Health and Human Services Estados Unidos Aportación neta de la UEn € 0,00 Dirección Independence avenue s. w. 200 20201 Washington d.c. Ver en el mapa Tipo de actividad Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Otras fuentes de financiación € 172 130,40
