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

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.

Statement of significance

In the eye, light sensing neural retina interacts and functions jointly with the underlying epithelial tissue (retinal pigment epithelium, RPE). Impairments in this physical interaction can cause retinal degeneration and blindness. However, currently we are missing cell culture model systems of the RPE and the retina, where this interaction could be manipulated and studied. To address this, we developed a hydrogel-based retina-mimicking structure cultured with RPE cells. This platform enabled studies of the interface, particularly the essential renewal process between the RPE and retinal photoreceptor cells. For the first time, we provided direct evidence that this process involves significant force transmission between the RPE and the retina. These findings uncover a previously unrecognized mechanobiological interaction between neural and epithelial cells in the eye.