Retina-on-chip: engineering functional in vitro models of the human retina using organ-on-chip technology

The retina is a complex and highly metabolic tissue in the back of the eye essential for human vision. Retinal diseases can lead to loss of vision in early and late stages of life, significantly affecting patients' quality of life. Due to its accessibility for surgical interventions and its isolated nature, the retina is an attractive target for novel genetic therapies and stem cell-based regenerative medicine. Understanding disease mechanisms and evaluating new treatments require relevant and robust experimental models. Retina-on-chip models are microfluidic organ-on-chip systems based on human tissue that capture multi-cellular interactions and tissue-level functions in vitro. Various retina-on-chip models have been described in literature. Some of them capture basic retinal barrier functions while others replicate key events underlying vision. In addition, some of these cellular systems have also been used in studies to explore their added value in retinal disease modeling. Most existing retina-on-chip models capture limited aspects of the phenotypic complexity of human diseases. This limitation arises primarily from the challenges related to controlled recapitulation of retinal function, including the relevant multi-cellular interactions and functional read-outs. In this review, we provide an update on recent advancements in the field of retina-on-chip, and we discuss the biotechnical strategies to further enhance the physiological relevance of the models. We emphasize that developers and researchers should prioritize the incorporation of the full spectrum of retinal complexity to effectuate a direct impact of retina-on-chip models in disease modeling and development of therapeutic strategies.