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

Autor: 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
Jazyk: angličtina
Rok vydání: 2003
Předmět:
Zdroj: Neurobiology of Disease, Vol 14, Iss 2, Pp 166-180 (2003)
Druh dokumentu: article
ISSN: 1095-953X
0969-9961
DOI: 10.1016/S0969-9961(03)00102-5
Popis: 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.
Databáze: Directory of Open Access Journals
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