title: Lack of alphavbeta5 integrin receptor or its ligand MFG-E8: distinct effects on retinal function.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Ophthalmology, Dyson Vision Research Institute, New York, NY 10065, USA.
authors.forename: Emeline F
authors.initials: EF
authors.lastname: Nandrot
authors.forename: Silvia C
authors.initials: SC
authors.lastname: Finnemann
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D018932:Chemokine CCL2 / Q000172:deficiency; D016207:Cytokines; D004195:Disease Models, Animal; D016023:Integrins / Q000378:metabolism*; D008024:Ligands; D008268:Macular Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008894:Milk Proteins / Q000378:metabolism*; D010857:Pigment Epithelium of Eye / Q000378:metabolism* / Q000648:ultrastructure; D054390:Receptors, CCR2 / Q000172:deficiency; D019707:Receptors, Chemokine / Q000172:deficiency
chemical_list: D000954:Antigens, Surface; D015415:Biomarkers; D000073883:CX3C Chemokine Receptor 1; C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; C471885:Cx3cr1 protein, mouse; D016207:Cytokines; D016023:Integrins; D008024:Ligands; C490919:Mfge8 protein, mouse; D008894:Milk Proteins; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; C403414:integrin alphavbeta8