Involvement of calcium in retinal pigment epithelial cell proliferation and pigmentation

L. Smith-Thomas, J. W. Haycock, R. Metcalfe, M. Boulton, S. Ellis, I. G. Rennie, P. S.R. Richardson, I. Palmer, M. A. Parsons, S. Mac Neil

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Purpose. The aim of this study is to explore the role of intracellular calcium in the mechanism of co-regulation of retinal pigment epithelial cells (RPE) by vitreous fluid and platelet mitogens, in order to evaluate the use of calcium modulating drugs in preventing RPE cell proliferation and contraction of fibrocellular membranes. Methods. Monolayers of human RPE cells were loaded with Fura-2-AM and examined in a fluorimeter for changes in intracellular free calcium in response to platelet mitogens (PDG-FAB or TGFβ1) and vitreous fluid (containing vitreous substrate proteins), both alone or in combination. The effect of the calcium antagonists TMB8 and verapamil and the calmodulin antagonists J8 and tamoxifen were then examined on RPE cell proliferation and pigmentation, both in the presence and absence of vitreous substrate and platelet mitogens. Results. We report that co-exposure of RPE cells to platelet mitogens and vitreous fluid produces an increase in intracellular free calcium of greater duration than that with either PDG-FAB, TGFβ1 or vitreous fluid alone. Calcium and calmodulin antagonists significantly reduce RPE cell proliferation in both the presence and absence of vitreous substrate and platelet mitogens. Calcium antagonists also stimulate the accumulation of autofluorescent granules within RPE cells. Conclusions. Calcium signalling plays a role in the co-regulation of RPE cells by vitreous substrate and platelet mitogens. Drugs that lower intracellular calcium or inhibit calmodulin may offer an additional approach to preventing the hyperproliferation of RPE cells in PVR.

Original languageEnglish (US)
Pages (from-to)813-822
Number of pages10
JournalCurrent Eye Research
Volume17
Issue number8
DOIs
StatePublished - Sep 2 1998
Externally publishedYes

Keywords

  • Calcium
  • Calmodulin
  • Human retinal pigment epithelial cells (HRPE)
  • Pigmentation
  • Proliferation

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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    Smith-Thomas, L., Haycock, J. W., Metcalfe, R., Boulton, M., Ellis, S., Rennie, I. G., Richardson, P. S. R., Palmer, I., Parsons, M. A., & Mac Neil, S. (1998). Involvement of calcium in retinal pigment epithelial cell proliferation and pigmentation. Current Eye Research, 17(8), 813-822. https://doi.org/10.1076/ceyr.17.8.813.5150