Abstract
BACKGROUND/AIMS: Diurnal phagocytosis of spent photoreceptor outer segment fragments by the retinal pigment epithelium (RPE) is critical for vision. We recently identified an important role for alphavbeta5 integrin receptors and their ligand Milk fat globule-EGF factor 8 (MFG-E8) in RPE phagocytosis. METHODS: We compared RPE phagocytosis and retinal function between mice deficient in alphavbeta5 integrin receptors and mice deficient in the secreted integrin ligand MFG-E8. RESULTS: Both beta5-/- and MFG-E8-/- mice exhibit the same phagocytic defect: RPE cells retain basal uptake activity but completely lack the burst of phagocytic activity as well as the rhythmic activation of Mer tyrosine kinase that follow circadian photoreceptor shedding in wild-type RPE. Strikingly, electroretinogram photoresponses decline with age only in beta5 -/- but not in MFG-E8-/- retina. CONCLUSION: These results identify a critical role of alphavbeta5 integrin receptors and their ligand MFG-E8 in synchronizing retinal phagocytosis. Additionally, we show that lack of alphavbeta5 receptors and MFG-E8 ligand have distinct consequences for retinal function. These intriguing results suggest that loss of phagocytic rhythm is not solely responsible for the age-related blindness of beta5-/- mice.