Identification of novel genes and altered signaling pathways in the retinal pigment epithelium during the Royal College of Surgeons rat retinal degeneration.
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.
CERTO, Equipe d'accueil n degrees 2502 du Ministère de la Recherche, Université René Descartes, Faculté de Médecine Necker, 156 rue de Vaugirard 75015 Paris, France.
Eric M
EM
Dufour
Emeline
E
Nandrot
Dominique
D
Marchant
Loïc
L
Van Den Berghe
Stéphanie
S
Gadin
Moussa
M
Issilame
Jean-Louis
JL
Dufier
Cécile
C
Marsac
Deborah
D
Carper
Maurice
M
Menasche
Marc
M
Abitbol
D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010587:Phagocytosis / Q000235:genetics; D010857:Pigment Epithelium of Eye / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011922:Rats, Mutant Strains; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D012374:Rod Cell Outer Segment / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics*
D018076:DNA, Complementary