Purchase this article with an account.
Anzor Gvritishvili, Yanling Liu, Joyce Tombran-Tink; High Glucose Alters bFGF Secretion by RPE Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5953.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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.
This PDF is available to Subscribers Only