TY - JOUR

T1 - Contributions of age-related alterations of the retinal pigment epithelium and of glia to the AMD-like pathology in OXYS rats

AU - Telegina, Darya V.

AU - Kozhevnikova, Oyuna S.

AU - Bayborodin, Sergey I.

AU - Kolosova, Nataliya G.

PY - 2017/1/30

Y1 - 2017/1/30

N2 - 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.

AB - 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.

KW - Animals

KW - Antigens, CD/metabolism

KW - Antigens, Differentiation, Myelomonocytic/metabolism

KW - Atrophy

KW - Biomarkers

KW - Calcium-Binding Proteins/metabolism

KW - Disease Models, Animal

KW - Gene Expression

KW - Glial Fibrillary Acidic Protein/genetics

KW - Humans

KW - Macrophages/metabolism

KW - Macular Degeneration/genetics

KW - Male

KW - Microfilament Proteins/metabolism

KW - Microglia/metabolism

KW - Microscopy, Fluorescence

KW - Neuroglia/metabolism

KW - Photoreceptor Cells, Vertebrate/metabolism

KW - Rats

KW - Retinal Pigment Epithelium/metabolism

KW - ALPHA-B-CRYSTALLIN

KW - MACULAR DEGENERATION

KW - MICROGLIA

KW - MICE

KW - MODEL

KW - ASTROCYTES

KW - FEATURES

KW - PROTECTS

KW - RETINOPATHY

KW - EXPRESSION

UR - http://www.scopus.com/inward/record.url?scp=85011021495&partnerID=8YFLogxK

U2 - 10.1038/srep41533

DO - 10.1038/srep41533

M3 - Article

C2 - 28134357

AN - SCOPUS:85011021495

VL - 7

SP - 41533

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 41533

ER -