The Retinal Pigment Epithelium: Cells That Know the Beat!

The retinal pigment epithelium (RPE) ensures different functions crucial for photoreceptor survival, and thus for vision, such as photoreceptor outer segments (POS) phagocytosis and retinal adhesion. Both follow a circadian rhythm with an activity peak occurring respectively 1.5-2 and 3.5 h after light onset. Interestingly, we showed that two rodent models, β5^-/- and Prpf31^+/- mice, display distinct alterations in both functions leading to different phenotypes. Indeed, the phagocytic peak totally disappears in β5 knockout mice but is attenuated and shifted in Prpf31^+/- mice. Conversely, the retinal adhesion peak only attenuated in β5^-/- mice is lost in Prpf31^+/- mice. These distinct alterations have different consequences on retinal homeostasis proportional to the observed defects: β5^-/- mice progressively lose vision and accumulate RPE lipofuscin deposits, while Prpf31^+/- mice develop RPE metabolic dysfunctions and gradual structural modifications indicative of cellular stress. Hence, animal models are useful to understand the importance of the proper regulation of these functions.