Identification of novel genes and altered signaling pathways in the retinal pigment epithelium during the Royal College of Surgeons rat retinal degeneration

Eric M Dufour; Emeline Nandrot; Dominique Marchant; Loïc Van Den Berghe; Stéphanie Gadin; Moussa Issilame; Jean-Louis Dufier; Cécile Marsac; Deborah Carper; Maurice Menasche; Marc Abitbol

Neurobiology of Disease (Nov 2003)

Identification of novel genes and altered signaling pathways in the retinal pigment epithelium during the Royal College of Surgeons rat retinal degeneration

Eric M Dufour,
Emeline Nandrot,
Dominique Marchant,
Loïc Van Den Berghe,
Stéphanie Gadin,
Moussa Issilame,
Jean-Louis Dufier,
Cécile Marsac,
Deborah Carper,
Maurice Menasche,
Marc Abitbol

Affiliations

Eric M Dufour: CERTO, Équipe d’accueil n°2502 du Ministère de la Recherche, Université René Descartes, Faculté de Médecine Necker, 156 rue de Vaugirard 75015 Paris, France; Section on Molecular Therapeutics, National Eye Institute, National Institutes of Health, Bethesda, MD, USA
Emeline Nandrot: CERTO, Équipe d’accueil n°2502 du Ministère de la Recherche, Université René Descartes, Faculté de Médecine Necker, 156 rue de Vaugirard 75015 Paris, France; Section on Molecular Therapeutics, National Eye Institute, National Institutes of Health, Bethesda, MD, USA
Dominique Marchant: CERTO, Équipe d’accueil n°2502 du Ministère de la Recherche, Université René Descartes, Faculté de Médecine Necker, 156 rue de Vaugirard 75015 Paris, France; Section on Molecular Therapeutics, National Eye Institute, National Institutes of Health, Bethesda, MD, USA
Loïc Van Den Berghe: CERTO, Équipe d’accueil n°2502 du Ministère de la Recherche, Université René Descartes, Faculté de Médecine Necker, 156 rue de Vaugirard 75015 Paris, France; Section on Molecular Therapeutics, National Eye Institute, National Institutes of Health, Bethesda, MD, USA
Stéphanie Gadin: CERTO, Équipe d’accueil n°2502 du Ministère de la Recherche, Université René Descartes, Faculté de Médecine Necker, 156 rue de Vaugirard 75015 Paris, France; Section on Molecular Therapeutics, National Eye Institute, National Institutes of Health, Bethesda, MD, USA
Moussa Issilame: CERTO, Équipe d’accueil n°2502 du Ministère de la Recherche, Université René Descartes, Faculté de Médecine Necker, 156 rue de Vaugirard 75015 Paris, France; Section on Molecular Therapeutics, National Eye Institute, National Institutes of Health, Bethesda, MD, USA
Jean-Louis Dufier: CERTO, Équipe d’accueil n°2502 du Ministère de la Recherche, Université René Descartes, Faculté de Médecine Necker, 156 rue de Vaugirard 75015 Paris, France; Section on Molecular Therapeutics, National Eye Institute, National Institutes of Health, Bethesda, MD, USA
Cécile Marsac: CERTO, Équipe d’accueil n°2502 du Ministère de la Recherche, Université René Descartes, Faculté de Médecine Necker, 156 rue de Vaugirard 75015 Paris, France; Section on Molecular Therapeutics, National Eye Institute, National Institutes of Health, Bethesda, MD, USA
Deborah Carper: CERTO, Équipe d’accueil n°2502 du Ministère de la Recherche, Université René Descartes, Faculté de Médecine Necker, 156 rue de Vaugirard 75015 Paris, France; Section on Molecular Therapeutics, National Eye Institute, National Institutes of Health, Bethesda, MD, USA
Maurice Menasche: CERTO, Équipe d’accueil n°2502 du Ministère de la Recherche, Université René Descartes, Faculté de Médecine Necker, 156 rue de Vaugirard 75015 Paris, France; Section on Molecular Therapeutics, National Eye Institute, National Institutes of Health, Bethesda, MD, USA
Marc Abitbol: CERTO, Équipe d’accueil n°2502 du Ministère de la Recherche, Université René Descartes, Faculté de Médecine Necker, 156 rue de Vaugirard 75015 Paris, France; Section on Molecular Therapeutics, National Eye Institute, National Institutes of Health, Bethesda, MD, USA

Journal volume & issue: Vol. 14, no. 2
pp. 166 – 180

Abstract

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Shed photoreceptor outer segments (POS) are phagocytosed by RPE cells in a circadian manner. The homozygous deletion of the c-mer gene abolishes the ingestion phase of this phagocytosis in the Royal College of Surgeons (RCS) rat strain, which in turn leads to the death of photoreceptor cells. We identified RPE transcripts for which the expression is modulated by the abrogation of POS phagocytosis. A microarray approach and the differential display (DDRT–PCR) technique revealed 116 modulated known genes, 4 modulated unknown genes, and 15 expressed sequenced tags (ESTs) corresponding to unknown genes. The microarray and DDRT–PCR analyses detected alterations in signaling pathways such as the phosphatidylinositol 3-kinase–Akt–mTOR pathway and the DLK/JNK/SAPK pathway. The abrogation of POS phagocytosis caused a decrease in endomembrane biogenesis and altered endocytosis, exocytosis, transcytosis, and several metabolic and signaling pathways in RCS RPE cells. We also found differential levels of transcripts encoding proteins involved in phagocytosis, vesicle trafficking, the cytoskeleton, retinoic acid, and general metabolism.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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