Abstract
Purpose: :
In proliferative ocular diseases, the retinal pigment epithelium (RPE) proliferates abnormally. Fibroblast growth factor 2 (FGF2) is an angiogenic factor that is found in hRPE cells. Octreotide is a somatostatin analogue that is known to inhibit human retinal pigment epithelial (hRPE) cell proliferation and FGF2 synthesis, but its effect on the FGF2 receptor (FGFR1) is unknown. We investigated the effect of octreotide on FGFR1 expression in hRPE cells.
Methods: :
hRPE cell cultures were grown in the presence of F12, fetal bovine serum (FBS) (1%), FBS (0.1%) or FBS (1%)+ octreotide (100 nM). Cell proliferation was measured by 3H-thymidine incorporation and trypan blue exclusion. FGFR1 synthesis was examined by immunocytochemistry using an anti-FGFR1 antibody.
Results: :
FBS (0-1%) stimulated H-thymidine incorporation and increased cell numbers in a dose-dependent manner. Octreotide (100nM) reduced FBS (1%)-stimulated 3H-thymidine incorporation from 4513±659 to 3775±521 CPM±SEM (p<.05, n=8). As determined with trypan blue exclusion, octreotide reduced cell counts from 4.7±0.6 to 2.9±0.3 cells/.1 uL ±SEM (p<.05, n=12). No blue cells were observed, indicating no cell death. Immunocytochemistry showed increased FGFR1 expression with increasing concentrations of FBS (0-1%). In addition, immunocytochemistry showed increased FGFR1 immunoreactivity in the presence of FBS (1%) compared to control, but FGFR1 expression decreased in the presence of FBS (1%) + octreotide (100nM) compared to FBS (1%).
Conclusions: :
FBS stimulates hRPE cell proliferation and FGFR1 synthesis. Octreotide inhibits FBS-stimulated hRPE cell proliferation as well as FGFR1 expression. We conclude that FGFR1 may mediate the inhibitory action of octreotide.
Keywords: growth factors/growth factor receptors • diabetic retinopathy • proliferative vitreoretinopathy