Recreating the retina Organoid modelling of disorders involving the optic nerve

Vision loss caused by diseases affecting the retina and optic nerve, such as glaucoma and albinism, poses a significant clinical challenge due to their complex pathogenesis and limited treatment options. This thesis presents the development of a human retinal organoid system as an in vitro model to study these disorders. A novel differentiation protocol was established to accelerate the generation of retinal ganglion cells (RGCs), significantly reducing the amount of time for these cells to develop. This system successfully recapitulated the cell types of the retina and key aspects of retinal development, and was further optimized using small molecules and signalling pathways to enhance organoid yield and cell-type specification. Using this organoid system, glaucoma and albinism development was modelled using patient-derived stem cells with disease-specific mutations. These models offered insights into pathogenesis and disruption to the retinal development. Additionally, an innovative approach towards constructing an in vitro optic nerve-like model, through the joining of retinal and brain organoids, demonstrated the potential of organoids to extend axonal bundles over long distances, with a focus on a future cell replacement therapy. This thesis not only provides new perspectives on the molecular mechanisms behind the development of optic nerve disorders, but also allows for future therapies and personalised medicine approaches. By advancing our retinal organoid methodology and integrating patient-specific genetic approaches, this research contributes significantly to our understanding of blinding diseases and the development of potential treatments and therapies for these debilitating diseases.