A project of the GIGA-Neurosciences awarded by the King Baudouin Foundation

A project of the GIGA-Neurosciences awarded by the King Baudouin Foundation

Retinal degeneration diseases, characterized by progressive loss of retinal cells, affect several million of persons worldwide and result in a progressive loss of visual abilities.

Currently, there is no effective treatment available for patients suffering from these conditions.

Recently, attention has been given to cell replacement therapy using retinal cells derived from induced Pluripotent Stem (iPS) cells. The first clinical trials are ongoing using stem cell-derived retinal epithelial cells in patients suffering from Age Related Macular Degeneration disease (AMD).

Transplantation of stem cell derived retinal cells offers great promise for the treatment of patient suffering from various retinal degeneration diseases. However, the treatment of pathologies of the neuro-retina remains more challenging as grafted cells need to establish neuronal connections with each other and the patient’s retina after implantation. Very little is known about the mechanisms that drive the formation of functional synaptic connections in the retina and the neuron circuit formation by transplanted neurons which is presently a major bottleneck in making iPS-derived neuro-retinal cells (including photoreceptor cells) useful in the clinic.

In this regard, this project aims to study and ultimately manipulate the process of synaptogenesis in a special in vitro system (embryoïd body (EB) based 3D retinal cultures) derived from mouse iPS-cells as a means towards enhancing functional recovery upon transplantation. This 3D culture system best recapitulates the normal development of the embryotic retinal tissue and offers the possibility to generate all retinal cell lineages in their properly layered configuration, hence recreating several structural features of the native retina. Using the most up-to-date single cell technologies and CRISPR/CAS9 methodology, this project will shed light on the fundamental mechanisms underlying synaptogenesis in the retina, which may lead to novel intervention strategies to foster functional recovery in patients.

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