Laminin-defined Mechanical Status Modulates Retinal Pigment Epithelium Functionality

Abstract

Epithelial cells are highly interconnected, whereby they acquire mesoscale mechanical properties to accomplish specific tissue functions. In homeostasis, these mechanical features can be summarised as mechanical homeostasis, regulated by the balance of intercellular tension and extracellular matrix adhesion forces. In the outer retina, the significance of these forces in defining its mechanical homeostasis and vision remains poorly understood. The retinal pigmented epithelium (RPE) is located at the base of the retina and supports vision by ensuring the light sensitivity and lifespan of photoreceptor cells. Due to different photoreceptor densities, this functional demand on the RPE varies from the most illuminated macula to the less illuminated retinal periphery and corresponds to a significant difference in monolayer organisation. In this work, we hypothesised that extracellular matrix cues define the relation between RPE organisation, mechanical status and functional demand. We found that the density of basement membrane laminin alpha 5 modulates RPE contractility levels which directly control the epithelium efficiency in phagocyting photoreceptor outer segments. In vivo, laminin alpha 5 density gradient follows retinal functional demand, thus supporting the physiological role of laminin alpha 5 in controlling RPE mechanical homeostasis. ECM-defined mechanical status of the RPE provides a novel parameter to consider for visual function and opens new paths of investigation for sight-threatening diseases such as high myopia and age-related macular degeneration.