Ziel
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.
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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Koordinator
B15 2TT Birmingham
Vereinigtes Königreich