April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
High Glucose Alters bFGF Secretion by RPE Cells
Author Affiliations & Notes
  • Anzor Gvritishvili
    Neural and Behavioral Science,
    Penn State College of Medicine, Hershey, Pennsylvania
  • Yanling Liu
    Neural and Behavioral Science,
    Penn State College of Medicine, Hershey, Pennsylvania
  • Joyce Tombran-Tink
    Neural and Behavioural Sciences,
    Penn State College of Medicine, Hershey, Pennsylvania
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 5953. doi:
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      Anzor Gvritishvili, Yanling Liu, Joyce Tombran-Tink; High Glucose Alters bFGF Secretion by RPE Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5953.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : We investigated the effects of high glucose on the retinal pigment epithelial cells to understand how glucose injured RPE cells may contribute to the development of diabetic retinopathy. A proteomics approach was used to study the effects of high glucose on the secretion of several cytokines by cultured RPE cells.

Methods: : Human ARPE19 cells were grown in various concentrations of glucose between 5.5-30 mM in medium containing 10% FBS. Cultures were maintained for > 45 days with fresh medium replaced every 4 days. RPE conditioned media (RPE-CM) was harvested immediately prior to medium change from cultures that were approximately 80% confluent and 50 ul of each supernatant subjected to luminex bead based assay of 30 different cytokines.

Results: : While there were minor changes among the cultures in the secretion of MCP1, IL-3, IL-2, IL-12, IFNg, VEGF, and PEDF, the strongest modulation was seen in the expression of basic fibroblast growth factor. bFGF levels in RPE-CM from cultures adapted to high glucose for >45 days were 1284, 8.85, 7.85 pg/ml in the 5.5, 22, and 30mM glucose conditions, respectively. This represents a >140 fold overall decrease in bFGF protein expression with increased glucose concentration. This change was accompanied by a constitutively higher level of phosphorylated PKCα in the high glucose exposed cultures compared to those grown in 5.5 mM.

Conclusions: : This study suggests that elevated glucose levels modulate secretion of bFGF by RPE cells and may do so through the activation of PKCα. Basic FGF is a well-characterized survival factor that provides protection from stress in the outer retina with receptors present on both RPE and photoreceptor cells. A decrease in secretion of bFGF by RPE cells in hyperglycemic conditions may alter the function of both cell types and an underlying mechanism in the development of diabetic retinopathy.

Keywords: retinal pigment epithelium • diabetic retinopathy • stress response 
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