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SG Baarsma, LJ Hofland, E Ter Avest, RW A M Kuijpers, J van Meurs, MP van Hagen; The Somatostatin Analog Octreotide Act as Growth Factor for Retinal Pigment Epithelium . Invest. Ophthalmol. Vis. Sci. 2002;43(13):702.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Retinal pigment epithelium (RPE)is a metabolic active layer that is essential for the maintenance of the neuroretina. Several retinal diseases are associated with an impairment of this cell layer such as retinitis pigmentosa and age-related macular degeneration (ARMD). Recently, we observed a benificial effect from the treatment of patients with exsudative ARMD with the somatostatin analog octreotide. Somatostatin analogs are potent inhibitors of the growth hormone secretion and subsequently the downstream IGF-1 synthesis. However,in order to investigate a direct role we measured the effect of octreotide on proliferation and VEGF production of human RPE. Methods: RPE cells were obtained from cadaver eyes and cultured in DMEM containing 20% FCS. The RPE cells were cultured with octreotide and with or without a combination of the growth factors, EGF,FGF and IGF-1, during 72 hrs. Because 5 different somatostatin receptors were cloned (sst1-5) we used RT-PCR to confirm the synthesis of these receptors in RPE and we measured also the expression of the ligands somatostatin-14 and cortistatin. Proliferation of RPE was measured by DNA synthesis and VEGF synthesis by an Elisa. Results: Octreotide stimulates the RPE proliferation significantly during culture with EGF. The VEGF production was enhanced by octreotide during proliferation, but has a tendency to be inhibited in non-proliferating RPE. Human RPE expresses the somatostatin receptors sst1 and sst2, somatostatin and also the somatostatin ligand "cortistatin. Conclusion: Octreotide stimulates the proliferation of activated RPE and the VEGF production during proliferation. The finding that human RPE produces two somatostatin ligands suggests an important autologic function of these neuropeptides in the regulation of RPE. More studies are warranted to investigate the role of these neuropeptides in diseased RPE.
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