BACKGROUND: Response to growth factors by the choriocapillaris is one of the main aspects in the development and progression of choroidal neovascularization in age-related macular degeneration (AMD). The aim of the study was to examine the effect of octreotide--an analogue of somatostatin with possible favorable effects in the treatment of age-related macular degeneration--on growth factor-activated bovine choriocapillary endothelial cells (BCEC). METHODS: Cultivated BCEC were stimulated with 20 ng/ml VEGF, 5 ng/ml bFGF, 50 ng/ml TGFbeta(2), or 50 ng/ml IGF-I for 24 h. Afterwards, the cells were incubated for a further 24 h with octreotide (10(-6) M). BCEC proliferation was determined by [(3)H]-thymidine incorporation. The experiments were performed in normal conditions and in O(2)-limited (5% O(2)) atmosphere. RESULTS: VEGF, bFGF, and IGF-I significantly stimulated BCEC proliferation under normoxic as well as under hypoxic conditions ( P<0.05); the value for TGFbeta(2)stimulation was not significant. Under normoxic conditions, after addition of octreotide to VEGF-, bFGF-, and IGF-I-stimulated cells there was no longer any significant [(3)H]-thymidine incorporation compared to the control medium. Under hypoxic conditions similar results were obtained after addition of octreotide to VEGF-, bFGF-, and IGF-I-stimulated cells. CONCLUSION: Octreotide has inhibitory properties after activation of BCEC with growth factors under normoxic and hypoxic conditions in vitro. Since activation of these cells is a crucial event in the development and progression of AMD, octreotide may be a potential drug for treatment of choroidal neovascularization in these patients.
BACKGROUND: Response to growth factors by the choriocapillaris is one of the main aspects in the development and progression of choroidal neovascularization in age-related macular degeneration (AMD). The aim of the study was to examine the effect of octreotide--an analogue of somatostatin with possible favorable effects in the treatment of age-related macular degeneration--on growth factor-activated bovine choriocapillary endothelial cells (BCEC). METHODS: Cultivated BCEC were stimulated with 20 ng/ml VEGF, 5 ng/ml bFGF, 50 ng/ml TGFbeta(2), or 50 ng/ml IGF-I for 24 h. Afterwards, the cells were incubated for a further 24 h with octreotide (10(-6) M). BCEC proliferation was determined by [(3)H]-thymidine incorporation. The experiments were performed in normal conditions and in O(2)-limited (5% O(2)) atmosphere. RESULTS:VEGF, bFGF, and IGF-I significantly stimulated BCEC proliferation under normoxic as well as under hypoxic conditions ( P<0.05); the value for TGFbeta(2)stimulation was not significant. Under normoxic conditions, after addition of octreotide to VEGF-, bFGF-, and IGF-I-stimulated cells there was no longer any significant [(3)H]-thymidine incorporation compared to the control medium. Under hypoxic conditions similar results were obtained after addition of octreotide to VEGF-, bFGF-, and IGF-I-stimulated cells. CONCLUSION:Octreotide has inhibitory properties after activation of BCEC with growth factors under normoxic and hypoxic conditions in vitro. Since activation of these cells is a crucial event in the development and progression of AMD, octreotide may be a potential drug for treatment of choroidal neovascularization in these patients.
Authors: Chung-Jung Chiu; Yvette P Conley; Michael B Gorin; Gary Gensler; Chao-Qiang Lai; Fu Shang; Allen Taylor Journal: Invest Ophthalmol Vis Sci Date: 2011-11-25 Impact factor: 4.799