Inhibitory Effect of Certain Neuropeptides on the Proliferation of Human Retinal Pigment Epithelial Cells

Abstract

Abstract: : Purpose: To define the effect of substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide, neuropeptide Y and secretoneurin on the proliferation of human retinal pigment epithelial cells Methods: ARPE-19 cells were used. The cells were standardly cultured in Dubecco's modified Eagle's medium (DMEM). One thousand and two thousand cells were incubated with the peptides for three and five days respectively, and the effect of the peptides was evaluated by an ATP-lite assay dose dependently. Furthermore, specific antagonists at 10-6M were used to find out whether the effect would be reversed. Results: Each of the peptides tested had an inhibiting effect. This inhibiting effect was weak but highly significant, averaging 10% to 15%, and was most pronouncedly seen at low concentrations between 10-10M and 10-14M. Each antagonist reversed the inhibiting effect fully. Conclusion: The present results clearly indicate that retinal pigment epithelial cells are under neural control and the low effective concentration of the peptides may be the one physiologically acting on these cells. The results are of important relevance both physiologically and pathophysiologically: physiologically, the inhibitory effect may mean that these peptides cause the cells to maintain in a differentiated condition. Pathophysiologically, the findings are relevant in proliferative vitreoretinopathy where retinal pigment epithelial cells proliferate in excess. The authors hypothesize that the inhibiting effect diminishes when these cells are swept out and actively migrate from their physiological location and thus, dedifferentiate and begin to proliferate. This hypothesis improves the knowledge on the initial processes in the pathogenesis of the disease as there seems to be a discrepancy between facilitatory and inhibitory influences favouring the former one in proliferative vitreoretinopathy. Furthermore, these neuropeptides constitute the first endogenous inhibitors of retinal pigment epithelial cell proliferation

Keywords: retinal pigment epithelium • proliferation • neuropeptides