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Petrus M. Van Hagen, R W. Kuijpers, S Swagemakers, T Missotten, F Staal, G S. Baarsma, L J. Hofland; The Somatostatin Analogue Octreotide Acts As A Vegf-c Stimulating Factor In Human Retinal Pigment Epithelium. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3356.
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Retinal pigment epithelium (RPE) has numerous functions that maintain the integrity and function of photoreceptors. Previously, we have shown that RPE cells express the somatostatin receptor subtypes (sst) 1 and 2. Moreover, sst2 activating drugs have been used in the treatment of retinal diseases such as diabetes, macular degeneration, retinitis pigmentosa and macular edema. In this study we investigated the effect of the sst2 agonist octreotide in RPE on cell growth, gene expression profiles and growth factor and cytokine synthesis/secretion.
Primary RPE cells were stably transduced with sst2a- LZRS-IRES-Lyt2a and incubated in DMEM with and without octreotide. Intracellular calcium flux experiments were used to confirm functionality of sst2. At time points 0 (baseline), 6 and 24 hours, gene-profile (Affymetrix, Santa Clara, CA) and growth factor and cytokine synthesis (RayBiotech, Norcross GA) were measured. Data analysis was performed with Partek and Treescape OmniViz. Cell proliferation was measured using whole DNA analysis and VEGF was measured by ELISA.
Gene expression profiles at 6 hrs and 24 hrs showed a change in expression of respectively 2870 and 249 genes (p<0.05) or 819 and 0 genes (p<0.01). Combined analysis of micro-array data at 6 hrs and growth factor and cytokine secretion spectrum at 24 hrs showed an increased VEGF-C expression/secretion pattern (and plasminogen activator/urokinase receptor and inhibin beta A). Co-culture of RPE cells with octreotide showed an increase secretion ratio VEGF/DNA from 0.4 to 1.2 pg/ng.
Combined gene expression profiles, protein blot results and culture experiments showed that octreotide stimulates VEGF(-C) production by RPE cells.
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