Abstract
It took 62 years from the description of the retinal dystrophy in rats from the Royal College of Surgeons (RCS) strain to the discovery of the molecular defect underlying the phenotype. Phagocytosis of photoreceptor outer segments (POS) by retinal pigment epithelial (RPE) cells follows a daily rhythm with a peak of activity 1.5–2 h after light onset for rod photoreceptors. We identified a deletion in the Mer tyrosine kinase (MerTK) receptor in RCS rat that abolishes internalization of POS by RPE cells. Accumulation of debris in the subretinal space then leads to drastic photoreceptor degeneration and rapid loss of vision. Interestingly, in wild-type mice and rats, MerTK is phosphorylated at the time of the phagocytic peak. We also demonstrated that the couple αvβ5 integrin receptor and MFG-E8 ligand synchronizes daily retinal phagocytosis. Indeed, when either one is absent in knockout mice, phagocytosis follows steady-state levels, and peak activation of integrin-associated protein and of MerTK does not occur. We now have a more precise picture of the sequence of molecular events governing retinal phagocytosis. However, requirement of MerTK ligands in vivo and linked signaling pathways still remain elusive so far.
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Acknowledgments
This work was supported by the following funding agencies, grants and awards: Ministère de l’Éducation Nationale, de la Recherche et de la Technologie, Université René Descartes, Faculté de Médecine Necker-Enfants Malades and Rétina France to the CERTO laboratory; Rétina France and Fondation pour la Recherche Médicale PhD grants, Fondation Bettencourt Schueller and Fondation Voir et Entendre Young Investigator grants to Emeline F. Nandrot; Rétina France and Fondation des Aveugles et Handicapés Visuels de France PhD grants to Eric M. Dufour; NIH grants EY13295, EY14184 and EY17173, Kirchgessner Research grant, William and Mary Greeve Scholarship by Research To Prevent Blindness, Inc., and Irma T. Hirschl Career Scientist Award to Silvia C. Finnemann.
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Nandrot, E.F., Dufour, E.M. (2010). Mertk in Daily Retinal Phagocytosis: A History in the Making. In: Anderson, R., Hollyfield, J., LaVail, M. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 664. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1399-9_16
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DOI: https://doi.org/10.1007/978-1-4419-1399-9_16
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