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Impressum
Effect of Octreotide in combination with growth factors on proliferation of bovine retinal endothelial cells in hypoxia.
Baldysiak-Figiel A., Kampmeier J., Lang G. E.
University of Ulm; Department of Ophthalmology, Germany.
Objective: Hypoxia is one of the clinical symptoms commonly occurring
in numerous ophthalmic disorders causing neovascularization and angiogenesis.
Other possible factors inducing proliferation of retinal endothelial cells
are various extracellular stimuli including hormones, cytokines and growth
factors. The aim of this study was to investigate the influence of octreotide,
an analogue of somatostatin, on IGF-1, bFGF, VEGF and TGF ß2 modulated
proliferation of bovine retinal endothelial cells (BREC) under hypoxic
conditions.
Methods: In the first series of experiments maximal effective concentrations
of growth factors and octreotide (10-5 to 10-10 M) were determined in
hypoxia. Subsequently, cells were maintained in O2 limited atmosphere
(5%) and treated with IGF-1 (50ng/ml), bFGF (10ng/ml), VEGF (20ng/ml)
and TGF ß2 (50ng/ml) alone or in combination with octreotide (10-6
M) and octreotide alone (10-6 M) for 24h in serum deprived medium containing
[3H]-thymidine. In all experiments untreated serum free negative controls
were used. Statistical analysis was performed using paired student's t-test.
Results: Under hypoxic conditions octreotide inhibited serum induced
proliferation of BREC only at the concentration of 10-6 M (p<0.02).
As compared to control octreotide (10-6 M) abolished IGF-1 and VEGF induced
proliferation (p<0.001) of BREC and showed significant inhibition of
proliferation induced by bFGF (p<0.001). Additionally, TGF ß2
treatment alone demonstrated an inhibitory effect (p<0.001) on BREC
proliferation which was not influenced by octreotide.
Conclusion: Our results suggest that various growth factors regulate
proliferation of bovine retinal endothelial cells in vitro. Furthermore,
octreotide is able to modulate the response of endothelial cells to VEGF,
IGF-1 and bFGF in hypoxia. Therefore, octreotide is a potential drug for
treatment of proliferative retinal disorders targeting neovascularization
and angiogenesis.
Supported by Rudolf and Clothilde Eberhardt-Stiftung and Pharmacia GmbH.