Oxygen modulates the response of the retinal pigment epithelium to basic fibroblast growth factor and epidermal growth factor by receptor regulation

A. Khaliq, J. Jarvis-Evans, D. McLeod, M. Boulton

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Purpose. To determine if low oxygen affects growth factor responsiveness in retinal pigment epithelial (RPE) cells and if such effects are mediated through changes in cell surface receptors. Methods. Proliferating human RPE cells were exposed to varying concentrations of exogenous basic fibroblast growth factor (bFGF) or epidermal growth factor (EGF) at different media oxygen tensions (16 to 147 mm Hg) and cell counts determined after 4 days. Receptor expression was determined by affinity cross-linking and saturation binding studies on confluent RPE cultures exposed to varying media oxygen tensions for 2 days. Results. Retinal pigment epithelial cells exhibited a greater proliferative response to exogenous growth factors at hypoxia than at higher media oxygen tensions, and they expressed bFGF and EGF receptors, which were upregulated under reduced oxygen tensions. Scatchard analysis demonstrated that hypoxia caused both an increase in the number of EGF receptors per cell and a shift from low to high affinity receptors. Conclusions. These results suggest that hypoxia not only can stimulate RPE cell proliferation per se, it also can 'prime' cells to respond more markedly to exogenous growth factors. These observations may be important in elucidating the cause of proliferative vitreoretinopathy.

Original languageEnglish (US)
Pages (from-to)436-443
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number2
StatePublished - 1996
Externally publishedYes

Fingerprint

Retinal Pigments
Retinal Pigment Epithelium
Fibroblast Growth Factor 2
Epidermal Growth Factor Receptor
Oxygen
Epithelial Cells
Intercellular Signaling Peptides and Proteins
Proliferative Vitreoretinopathy
Cell Surface Receptors
Epidermal Growth Factor
Cell Count
Cell Proliferation
Hypoxia

Keywords

  • basic fibroblast growth factor
  • epidermal growth factor
  • hypoxia
  • oxygen
  • receptors
  • retinal pigment epithelial cells

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Oxygen modulates the response of the retinal pigment epithelium to basic fibroblast growth factor and epidermal growth factor by receptor regulation. / Khaliq, A.; Jarvis-Evans, J.; McLeod, D.; Boulton, M.

In: Investigative Ophthalmology and Visual Science, Vol. 37, No. 2, 1996, p. 436-443.

Research output: Contribution to journalArticle

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AU - Jarvis-Evans, J.

AU - McLeod, D.

AU - Boulton, M.

PY - 1996

Y1 - 1996

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AB - Purpose. To determine if low oxygen affects growth factor responsiveness in retinal pigment epithelial (RPE) cells and if such effects are mediated through changes in cell surface receptors. Methods. Proliferating human RPE cells were exposed to varying concentrations of exogenous basic fibroblast growth factor (bFGF) or epidermal growth factor (EGF) at different media oxygen tensions (16 to 147 mm Hg) and cell counts determined after 4 days. Receptor expression was determined by affinity cross-linking and saturation binding studies on confluent RPE cultures exposed to varying media oxygen tensions for 2 days. Results. Retinal pigment epithelial cells exhibited a greater proliferative response to exogenous growth factors at hypoxia than at higher media oxygen tensions, and they expressed bFGF and EGF receptors, which were upregulated under reduced oxygen tensions. Scatchard analysis demonstrated that hypoxia caused both an increase in the number of EGF receptors per cell and a shift from low to high affinity receptors. Conclusions. These results suggest that hypoxia not only can stimulate RPE cell proliferation per se, it also can 'prime' cells to respond more markedly to exogenous growth factors. These observations may be important in elucidating the cause of proliferative vitreoretinopathy.

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