Biomimetic hydrogel platform reveals active force transduction from retinal pigment epithelium to photoreceptors

Abstract In the eye, the retinal pigment epithelium (RPE) maintains the functionality and welfare of retinal photoreceptors and forms a tight, interlocked structure with photoreceptor outer segments (POSs). The RPE-retina interaction is difficult to recapitulate in vitro , limiting the studies addressing the retinal maintenance functions of the RPE. To overcome this challenge, we constructed a retina-mimicking structure using a soft polyacrylamide hydrogel coated with Matrigel. This structure was introduced to RPE cells’ apical side to model the RPE-retina interface in vitro . As a result, RPE cells attached to the hydrogels during culture, enabling further studies of cell adhesion and force transduction between the RPE-hydrogel with rheology and traction force microscopy. These methods were applied to a critical interactive process between the retina and the RPE: phagocytosis of the aged tips of POSs enabling their renewal. During phagocytosis, RPE cells imposed considerable traction forces to the POS particles. The force generation was actin-dependent, and the forces were significantly reduced by the disruption of RPE’s actin cytoskeleton. These results add another layer to the diverse interaction mechanisms between the RPE and the neural retina and pave the way for further studies of the RPE-retina interplay.