Octreotide inhibits growth factor-induced bovine choriocapillary endothelial cells in vitro

Spraul, Christoph W.; Baldysiak-Figiel, Alicja; Lang, Gerhard K.; Lang, Gabriele E.

doi:10.1007/s00417-002-0441-7

Cited by 36 publications

(24 citation statements)

References 25 publications

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“…This rather selective action of octreotide on growth factor-controlled endothelial cell proliferation could also explain why octreotide is ineffective in treating non-proliferative retinopathies which are not evoked by growth factor overproduction (van Hagen et al 2000). In further support of this view, other recent studies found that inhibition of neovascularization by octreotide results from a direct inhibition of bFGF or IGF-1 activity on endothelial cells (Grant et al 1993a, Danesi et al 1997, Spraul et al 2002.…”

Section: Discussionsupporting

confidence: 53%

Octreotide prevents growth factor-induced proliferation of bovine retinal endothelial cells under hypoxia

Baldysiak-Figiel

Lang²,

Kampmeier³

et al. 2004

Journal of Endocrinology

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Ocular diseases such as proliferative diabetic retinopathy are the major cause of blindness in industrialized countries. The main pathologic features of these diseases are hypoxia and overproduction of growth factors resulting in pathologic proliferation of endothelial cells and new vessel formation. Particularly, hypoxia and growth factors, such as VEGF, IGF-1, bFGF and TGF 2 , show a complex interaction in the onset and progression of the diseases. Therefore, to date, most therapeutic strategies for proliferative retinopathies have targeted proliferation of endothelial cells evoked by growth factors. Recently, a synthetic analog of somatostatin, octreotide, has been shown to inhibit the proliferation of various cells in vitro, including endothelial cells. In this study, we have investigated the proliferative response of bovine retinal endothelial cells (BREC) to growth factors under hypoxic conditions and the modulation by octreotide. We found a dose-dependent increase of cell proliferation with VEGF, IGF-1 and bFGF, and inhibition of hypoxia-induced cell proliferation with TGF 2 . Moreover, growth factorinduced, but not hypoxia-induced, cell proliferation was attenuated in the presence of octreotide. In contrast, TGF 2 abolished hypoxia-induced BREC proliferation. Similar to octreotide BIM23027, a somatastatin receptor subtype 2 (SSTR2) receptor agonist was able to attenuate the growth factor-induced proliferation of BREC expressing mRNA and protein for SSTR2. Therefore, we postulate that octreotide exerts its effects mainly through binding to the SSTR2. Taken together, our findings point to octreotide as a promising candidate for the treatment of eye disorders involving growth factor-dependent proliferation of endothelial cells.

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Section: Discussionsupporting

confidence: 53%

Octreotide prevents growth factor-induced proliferation of bovine retinal endothelial cells under hypoxia

Baldysiak-Figiel

Lang²,

Kampmeier³

et al. 2004

Journal of Endocrinology

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“…Octreotide inhibits the proliferation of choriocapillary endothelial cells in response to IGF-1 and VEGF release in vitro and in vivo [42,43] , it exerts its function by inhibiting the IGF-1 signal transduction pathway. Our data support the hypothesis that octreotide exerts its anti-angiogenic effects mainly through via the VEGF/ IGF-1 pathway.…”

Section: Discussionmentioning

confidence: 99%

Octreotide Inhibits Choroidal Neovascularization in Rats

Zhang²,

Xu³

et al. 2009

Ophthalmic Res

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Aims: Octreotide exhibits anti-angiogenic activity in animal models of retinopathy of prematurity and in clinical cases of proliferative diabetic retinopathy. In this study, we tested the applicability of using octreotide for inhibiting experimental choroidal neovascularization (CNV) in rats. Methods: Of 15 adult rats used, 3 served as non-laser-treated controls. CNV was induced in the right eye of the remaining 12 rats by laser photocoagulation. These 12 rats were divided into two groups (n = 6 each) which were retrobulbarly injected with octreotide (50 μg/kg) or phosphate-buffered saline (PBS) (0.15 ml) immediately and on day 3 after the first injection. Fluorescein angiography and quantitative analysis of the retinal pigment epithelium (RPE)-choroidal flat mounts were performed 14 days after the operation to evaluate the changes in the CNV lesions. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was used to compare the changes shown by the octreotide-, PBS-, and non-laser-treated rats (n = 3 each) with regard to mRNA levels of the vascular endothelial growth factor (VEGF) and insulin-like growth factor (IGF)-1 in the RPE-choroidal complex. Results: Octreotide treatment significantly inhibited fluorescein leakage and the extent of neovascularization as was observed in the flat mounts of choroidal tissue derived from the rats with induced CNV. The VEGF and IGF-1 mRNA levels were reduced following treatment with octreotide. Conclusion: The retrobulbar administration of octreotide may be an effective new therapeutic strategy for CNV.

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“…This suggests an autocrine function of IGF-1 in the normal human retina and may point toward a role for the IGF axis in the pathogenesis of neovascular AMD. 15 It has also been shown that the IGF axis can contribute to angiogenesis directly by increasing proliferation of retinal endothelial cells, 77,78 or indirectly through inducing vascular endothelial growth factor (VEGF) gene expression of cultured RPE cells. 79 Furthermore, inhibitors of IGF1R, such as somatostatin and picropodophyllin, 14,80 reduce IGF-1-dependent VEGF expression in human RPE cells and in vivo mouse model, respectively.…”

Section: Discussionmentioning

confidence: 99%

Associations between Genetic Polymorphisms of Insulin-like Growth Factor Axis Genes and Risk for Age-Related Macular Degeneration

Chiu

Conley

Gorin

et al. 2011

Invest. Ophthalmol. Vis. Sci.

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Octreotide inhibits growth factor-induced bovine choriocapillary endothelial cells in vitro

Cited by 36 publications

References 25 publications

Octreotide prevents growth factor-induced proliferation of bovine retinal endothelial cells under hypoxia

Octreotide prevents growth factor-induced proliferation of bovine retinal endothelial cells under hypoxia

Octreotide Inhibits Choroidal Neovascularization in Rats

Associations between Genetic Polymorphisms of Insulin-like Growth Factor Axis Genes and Risk for Age-Related Macular Degeneration

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