Optical imaging of retinal function for gene and cell therapies

Title Optical imaging of retinal function for gene and cell therapies
Start date 2021-04-01
End date 2026-03-31
Sponsor European Research Council - Consolidator Grant (ERC-CoG)

Associated cell lines

Project Description

For patients suffering from inherited retinal diseases (IRDs), gene and cell therapies offer hope of preserving vision. Suitable high resolution imaging tools that allow in vivo testing of individual cells are currently lacking yet are essential to develop these therapies. Imaging is crucial, firstly in the deep phenotyping of the diseases to determine which retinal cell layers are degenerated and devise an appropriate therapeutic path, then in the lab for in vitro therapy development, and finally to monitor therapeutic success by following up on the preservation or restoration of retinal cell structure and function in patients over time. My group develops novel optical imaging tools for non-invasive 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 method to detect metabolic contrast: dynamic FFOCT detects intracellular organelle motion to indicate cell activity. This project aims to take these imaging methods beyond their current structural imaging capability to achieve quantitative functional assessment of cellular activity in vivo and in vitro. Specifically, I aim to develop new non-invasive all-optical tools to provide simultaneous subjective and objective retinal function measurements for the first time. I will adapt existing optical setups based on dynamic FFOCT and AOO to allow retinal stimulation with visible light to perform functional testing of i) in vivo 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 which are rendered light sensitive via optogenetics; ii) in vivo patients being treated in our clinical centre with novel gene and cell therapies to check that vision is being successfully preserved or restored.