EFFECT OF OCTREOTIDE IN COMBINATION WITH GROWTH FACTORS ON PROLIFERATION OF BOVINE RPE CELLS IN VITRO

97th DOG Annual Meeting 1999

K435
EFFECT OF OCTREOTIDE IN COMBINATION WITH GROWTH FACTORS ON PROLIFERATION OF BOVINE RPE CELLS IN VITRO

J. Amann, C. Kaven, C. W. Spraul, G. K. Lang, G. E. Lang

The long-acting somatostatin analogue octreotide is used as a therapy for patients with diabetic retinopathy and age-related macular degeneration. Growth factors, such as EGF, bFGF, VEGF, and PDGF have been implicated to be involved in the pathogenesis of these diseases. The aim of this study was to investigate the effect of octreotide on growth factor induced proliferation of bovine retinal pigment epithelial (RPE) cells in vitro.

Methods: RPE cells were assayed for proliferation as measured by [³H]-thymidine uptake (ccpm). Bovine RPE cells at passage 3-8 were seeded in a 96-well plate and incubated for a 24 hour period with a minimum-medium followed by an incubation of 24 hours with the different growth factors at a concentration of 10ng/ml alone and together with 5x10 ^-5 M octreotide. Afterwards the cells were pulsed with 5µCi/ml [³H]-thymidine for 12 hours, the incorporated radioactivity was measured on glasfiberfilters in a beta-counter [mean ccpm]. The Wilcoxon Signed Rank-test was used for statistical analyses.

Results: Exposure of RPE cells to PDGF (19804ccpm) and bFGF (3358ccpm) resulted in a significantly higher proliferation compared to control medium (1543ccpm) (p<0.05). No difference was found for EGF (2326ccpm) (p=0.06). For VEGF (771ccpm) and octreotide (302ccpm) a significant reduction in RPE cell proliferation as well as for the combination ofVEGF with octreotide (75ccpm) (p<0.05) was found. There was a significant reduction in proliferation of RPE cells with PDGF, bFGF, and EGF in combination with octreotide versus growth factors alone (octreotide in combination with PDGF 308ccpm, with bFGF 229ccpm, with EGF 222ccpm, with VEGF 75ccpm) (p<0.005).

Conclusion: The data suggest that octreotide inhibits RPE cell proliferation of bovine RPE cells and eliminates the PDGF and bFGF induced stimulation of RPE cell proliferation. An enhanced inhibitory effect is found for the combination of octreotide and VEGF. Octreotide may be a new useful drug in the treatment of diseases in which RPE cell proliferation is involved.

University of Ulm; Department of Ophthalmology

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