title: Contributions of age-related alterations of the retinal pigment epithelium and of glia to the AMD-like pathology in OXYS rats.
abstract: Age-related macular degeneration (AMD) is a major cause of blindness in developed countries, and the molecular pathogenesis of early events of AMD is poorly understood. It is known that age-related alterations of retinal pigment epithelium (RPE) cells and of glial reactivity are early hallmarks of AMD. Here we evaluated contributions of the age-related alterations of the RPE and of glia to the development of AMD-like retinopathy in OXYS rats. We showed that destructive alterations in RPE cells are a primary change during the development of retinopathy in OXYS rats. Furthermore, a defect of retinal maturation and decreased immune function at the preclinical stage of retinopathy were observed in OXYS rats in addition to the impairment of RPE cell proliferation and of their capacity for division. At the active stage of the disease, the atrophic alterations increased, and reactive gliosis was observed when disease progressed, but immune function stayed weakened. Unexpectedly, we did not observe migration of microglia and macrophages into the photoreceptor layer. These results and the wide spectrum of age-related retinal alterations in humans as well as individual differences in the risk of AMD may be attributed to genetic factors and to differences in the underlying molecular events.
authors.affiliation: Institute of Cytology and Genetics SB RAS, Novosibirsk 630090, Russia.
authors.forename: Darya V
authors.initials: DV
authors.lastname: Telegina
authors.affiliation: Institute of Cytology and Genetics SB RAS, Novosibirsk 630090, Russia.
authors.forename: Oyuna S
authors.initials: OS
authors.lastname: Kozhevnikova
authors.affiliation: Institute of Cytology and Genetics SB RAS, Novosibirsk 630090, Russia.
authors.forename: Sergey I
authors.initials: SI
authors.lastname: Bayborodin
authors.affiliation: Institute of Cytology and Genetics SB RAS, Novosibirsk 630090, Russia.|Novosibirsk State University, Novosibirsk 630090, Russia.
authors.forename: Nataliya G
authors.initials: NG
authors.lastname: Kolosova
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001284:Atrophy; D015415:Biomarkers; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008268:Macular Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D008856:Microscopy, Fluorescence; D009457:Neuroglia / Q000378:metabolism*; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology; D051381:Rats; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000473:pathology*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; C100745:Aif1 protein, rat; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C000614142:Gfap protein, rat