title: Receptor MER Tyrosine Kinase Proto-oncogene (MERTK) Is Not Required for Transfer of Bis-retinoids to the Retinal Pigmented Epithelium.
abstract: Accumulation of bis-retinoids in the retinal pigmented epithelium (RPE) is a hallmark of aging and retinal disorders such as Stargardt disease and age-related macular degeneration. These aberrant fluorescent condensation products, including di-retinoid-pyridinium-ethanolamine (A2E), are thought to be transferred to RPE cells primarily through phagocytosis of the photoreceptor outer segments. However, we observed by two-photon microscopy that mouse retinas incapable of phagocytosis due to a deficiency of the c-Mer proto-oncogene tyrosine kinase (Mertk) nonetheless contained fluorescent retinoid condensation material in their RPE. Primary RPE cells from Mertk-/-mice also accumulated fluorescent products in vitro Finally, quantification of A2E demonstrated the acquisition of retinal condensation products in Mertk-/-mouse RPE prior to retinal degeneration. In these mice, we identified activated microglial cells that likely were recruited to transport A2E-like condensation products to the RPE and dispose of the dying photoreceptor cells. These observations demonstrate a novel transport mechanism between photoreceptor cells and RPE that does not involve canonical Mertk-dependent phagocytosis.
authors.affiliation: From Polgenix, Inc. and.
authors.forename: Grazyna
authors.initials: G
authors.lastname: Palczewska
authors.affiliation: the Departments of Ophthalmology and Visual Sciences and aam19@case.edu.
authors.forename: Akiko
authors.initials: A
authors.lastname: Maeda
authors.affiliation: Pharmacology and Cleveland Center for Membrane and Structural Biology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106.
authors.forename: Marcin
authors.initials: M
authors.lastname: Golczak
authors.affiliation: the Departments of Ophthalmology and Visual Sciences and.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Arai
authors.affiliation: From Polgenix, Inc. and.
authors.forename: Zhiqian
authors.initials: Z
authors.lastname: Dong
authors.affiliation: the Departments of Ophthalmology and Visual Sciences and.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Perusek
authors.affiliation: Pharmacology and Cleveland Center for Membrane and Structural Biology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106.
authors.forename: Brian
authors.initials: B
authors.lastname: Kevany
authors.affiliation: Pharmacology and Cleveland Center for Membrane and Structural Biology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106 kxp65@case.edu.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Palczewski
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000429:Alcohol Oxidoreductases / Q000502:physiology*; D000818:Animals; D008264:Macrophages; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia; D010587:Phagocytosis; D010786:Photoreceptor Cells / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D012176:Retinoids / Q000378:metabolism*; D000076202:c-Mer Tyrosine Kinase
chemical_list: D018528:ATP-Binding Cassette Transporters; D000429:Alcohol Oxidoreductases; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D012176:Retinoids; D000076202:c-Mer Tyrosine Kinase; C512841:Abca4 protein, mouse; C525880:HSD17B6 protein, mouse; C490767:Mertk protein, mouse
keywords: retina; retinal degeneration; retinal metabolism; rhodopsin; vitamin A