Retinal Development and Organoids
Starting with either embryonic stem cells or induced pluripotent stem cells, we can generate mini-retinas entirely in vitro. These retinal organoids represent a highly accessible system for studies of retinal development and disease. They accurately mirror early stages of human retinogenesis in a stepwise, temporal sequence, and the development of major classes of retinal neurons is recapitulated
An example of a layered organoid with RGCs in green (in the middle) and photo-receptors in magenta (forming an outer nuclear layer)
Organoids have been especially successful in facilitating the differentiation and maturation of the cells in the outer retina, ie. the photoreceptors, which develop their characteristic morphology and gene expression.
Organoid with cone opsin labeling
However, we do not know whether the cells and circuits of the inner retina (bipolar cells and amacrine cells) develop in the retinal organoids as they do in vivo. We are currently using a number of approaches to study inner retinal development in organoids including Diolistic labeling (in collaboration with Drs. Chi Zhang and Rachel Wong, shown to the right), serial block face scanning EM, single cell RNAseq (in collaboration with the Trapnell lab) and electrophysiological recordings (in collaboration with the Rieke lab).