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

Retinal pigment epithelium (RPE) is an epithelial monolayer located at the back of the eye underneath the neural retina. RPE and retina interact closely, with RPE performing multiple tasks to ensure proper retinal physiology and forming a tight, interlocked structure with photoreceptor outer segments (POS). Essential for retinal welfare, RPE enables the daily renewal of POS by phagocytosing their aged tips. Current RPE in vitro cell culture systems lack the contact between RPE and retina, possibly limiting not only RPE maturation but also hindering the studies addressing the RPE-retina interactions. We constructed a retina-mimicking structure from a soft polyacrylamide hydrogel with Matrigel coating and introduced it to RPE cells’ apical side during culturing to model the RPE-retina interface in vitro . RPE cells adhered to the hydrogels during culture, enabling further studies of the biophysical properties of the RPE-hydrogel interface with methods utilizing rheology and traction force microscopy. During phagocytosis, RPE cells generated considerable traction forces that were followed using a hydrogel coated with POS particles. Disruption of RPE’s actin cytoskeleton with Cytochalasin D significantly reduced the force generation. These results support the view of RPE as a mechanically active partner for retina. In addition, our retina-mimicking structure offers a tool for further biophysical modeling of the RPE-retina interface.