GSE173180
Enhancing human iPSC-derived retinal organoids by incorporating microglia-like cells
Microglia are the primary resident immune cells in the retina. They regulate neuronal survival and synaptic pruning, which makes them essential for normal development. Following injury, they mediate adaptive responses and under pathological conditions can trigger neurodegeneration exacerbating the effect of the disease. Retinal organoids derived from human induced pluripotent stem cells (hiPSCs) are increasingly used for a range of applications, including disease modelling, development of new therapies and in the study of retinogenesis. Despite their close resemblance to the in vivo retina, they lack some key physiological features including immune cells. To enhance the retinal organoid model, we engineered an hiPSC co-culture system containing the hiPSC-derived retinal organoids and hiPSC-derived microglia-like (iMG) cells and tested their retinal invasion capacity and function. We incorporated iMG into retinal organoids at 13 weeks and tested their effect on function and development at 15 and 21.5 weeks of differentiation. Our key findings showed that iMG cells were able to respond to endotoxin challenge in monocultures and when co-cultured with the organoids. Single cell RNA-Seq transcriptomic analyses, protein expression, electron microscopy imaging and electrophysiological recordings showed that retinal organoids developed normally, expressed key markers, and retained their ability to generate spiking activity in response to light. Thus, this new co-culture immunocompetent in vitro retinal model provides a platform with greater relevance to the in vivo human retina. Overall design: We engineered an hiPSC co-culture system containing the hiPSC-derived retinal organoids and hiPSC-derived microglia-like (iMG) cells and tested their retinal invasion capacity and function.