Retina organoids: Window into the biophysics of neuronal systems

With a kind of magnetism, the human retina draws the eye of neuroscientist and physicist alike. It is attractive as a self-organizing system, which forms as a part of the central nervous system via biochemical and mechanical cues. The retina is also intriguing as an electro-optical device, converting photons into voltages to perform on-the-fly filtering before the signals are sent to our brain. Here, we consider how the advent of stem cell derived in vitro analogs of the retina, termed retina organoids, opens up an exploration of the interplay between optics, electrics, and mechanics in a complex neuronal network, all in a Petri dish. This review presents state-of-the-art retina organoid protocols by emphasizing links to the biochemical and mechanical signals of in vivo retinogenesis. Electrophysiological recording of active signal processing becomes possible as retina organoids generate light sensitive and synaptically connected photoreceptors. Experimental biophysical tools provide data to steer the development of mathematical models operating at different levels of coarse-graining. In concert, they provide a means to study how mechanical factors guide retina self-assembly. In turn, this understanding informs the engineering of mechanical signals required to tailor the growth of neuronal network morphology. Tackling the complex developmental and computational processes in the retina requires an interdisciplinary endeavor combining experiment and theory, physics, and biology. The reward is enticing: in the next few years, retina organoids could offer a glimpse inside the machinery of simultaneous cellular self-assembly and signal processing, all in an in vitro setting.