Oxygen modulates the response of the retinal pigment epithelium to basic fibroblast growth factor and epidermal growth factor by receptor regulation.
OBJECTIVE
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 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 t respond more markedly to exogenous growth factors. These observations may be important in elucidating the cause of proliferative vitreoretinopathy.
Khaliq
A
A
Department of Ophthalmology, University of Manchester, England.
Jarvis-Evans
J
J
McLeod
D
D
Boulton
M
M
D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D008970:Molecular Weight; D010100:Oxygen / Q000494:pharmacology*; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000737:chemistry / Q000378:metabolism*
D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D010100:Oxygen