Optical imaging of retinal function for gene and cell therapies
For patients suffering from inherited retinal diseases (IRDs), gene and cell therapies offer hope of preserving or restoring vision. Retinal imaging is crucial, to first phenotype patients to determine which cells are degenerated and devise an appropriate therapeutic path; then in the lab for cell therapy development, and finally back in the clinic to monitor therapeutic success in patients who have been treated with gene or cell therapy. To date, the imaging tools used in the clinic do not provide sufficient resolution for visualizing individual cells non-invasively, constituting a major roadblock for the development of gene and cell therapies. 
My group develops novel optical imaging tools for noninvasive cellular imaging such as full field optical coherence tomography (FFOCT), an interferometric technique, and adaptive optics ophthalmoscopy (AOO), which corrects ocular aberrations, to achieve diffraction limited resolution of in vivo retina. Recently we also devised a dynamic FFOCT method to detect metabolic contrast using intracellular organelle motion to indicate cell activity. These new noninvasive, all optical tools have the potential to provide, for the first time, simultaneous subjective and objective retinal function measurements. Here, I propose to adapt these existing optical setups based on dynamic FFOCT and AOO to allow retinal stimulation with visible light to enable functional testing of i) patients with IRDs in order to evaluate surviving cells and orient their therapy path; ii) in vitro retinal organoids derived from induced pluripotent stem cells; ii) patients being treated in our clinical centre with novel gene and cell therapies to check that vision is being successfully preserved or restored.
The new imaging methods developed here will achieve quantitative functional assessment of cellular activity in vivo and in vitro, lifting the major imaging obstacles for successful application of gene and cell therapies in the clinic.