Premium
High Glucose Promotes the Pro‐Migratory Phenotype of Retinal Pigment Epithelial Cells through Increased Oxidative Stress
Author(s) -
Farnoodian Mitra,
Sorenson Christine M,
Sheibani Nader
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.969.20
Subject(s) - microbiology and biotechnology , retinal pigment epithelium , blood–retinal barrier , biology , oxidative stress , retinal , endocrinology , diabetic retinopathy , diabetes mellitus , biochemistry
Defects in the outer blood‐retinal barrier have significant impact on pathogenesis of diabetic retinopathy and macular edema. However, the detailed mechanisms involved remain largely unknown. This is, in part, attributed to the lack of suitable animal and cell culture models, including those of mouse origin for such studies. The mouse models provide the ability to test the impact of various genes with important functions in ocular homeostasis in diabetes and its complications. We recently reported a method for culture of mouse retinal pigment epithelial (RPE) cells from wild type and transgenic mice. The RPE cells are responsible for maintaining the integrity of outer blood‐retinal barrier whose dysfunction during diabetes has significant impact on vision. Here we determined the impact of high glucose conditions on the function of RPE cells. We showed that high glucose conditions minimally impacted the proliferation and apoptosis of both human and mouse RPE cells, but these cells were more migratory and exhibited increased levels of oxidative stress. High glucose minimally affected the cell‐matrix and cell‐cell interactions of RPE cells. However, the expression of integrins and extracellular matrix proteins including tenascin C, thrombospondin‐1 and pigmented epithelium derived factor were increased under high glucose conditions. These cells also exhibited increased nuclear localization of anti‐oxidant transcription factor Nrf2 and reduced phagocytic activity under high glucose conditions. Furthermore, high glucose minimally affected the level vascular endothelial growth factor and activity of AKT, MAPK, and Src kinase signaling pathways. However, incubation of RPE cells under high glucose conditions with anti‐oxidant N‐acetylcysteine restored their normal migratory activity. Thus, high glucose promotes a pro‐inflammatory and oxidative state of RPE cells without a significant effect on their proliferation and apoptosis. The increased migration of RPE cells under high glucose condition is consistent with increased susceptibility to choroidal neovascularization with diabetes. Support or Funding Information NIH R24 EY022883; NIH P30 EY016665; NIH R21 EY023024