Live Imaging Microscopy of Human Retina Organoids: Photoreceptor Pathology

Neurodegenerative diseases involve many different (sub)cellular pathologic processes like mitochondria damage, which are still incompletely understood and present future targets for therapy development. Live imaging microscopy of dynamic pathologic changes at single cell resolution might advance studies of pathomechanisms and biomarkers. Organoid technologies may complement and facilitate animal and patient studies: We recently reported a novel pathomechanism of photoreceptor degeneration via cell extrusion, identified and validated by live imaging in human retina organoids. Here, we describe the related workflow for live imaging organoid studies. As another use-case, we describe mitochondrial alterations in photoreceptors acutely damaged by the ionophore CCCP. Our data further support a CCCP-induced experimental model for photoreceptor pathology, which can be monitored by JC-1 live dye-assisted live imaging. Thus, we demonstrate that live imaging advances studies of early subcellular pathologic events in human organoids. Such approaches might facilitate future therapeutic target identification and development for early intervention.