OXYGEN MODULATES PRODUCTION OF BFGF AND TGF-BETA BY RETINAL CELLS IN-VITRO

Vasoproliferative retinopathies result from retinal capillary non-perf usion and consequent inner retinal hypoxia, However, it is not known w hether oxygen mediates vasoproliferation directly (at the nuclear leve l) or indirectly by regulating the production of growth factors. We ha ve investigated the effect of oxygen on the production of basic fibrob last growth factor and transforming-growth-factor-beta by a variety of retinal cell types in culture, Confluent cultures were maintained for 48 hr under varying oxygen tensions ranging from 135 to 18 mmHg. A re duction in basic fibroblast growth factor levels was observed in the c ell lysates and extracellular matrix from retinal microvascular endoth elial cell, retinal microvascular pericyte and retinal pigment epithel ial cell cultures when the oxygen tension of the medium was reduced fr om 135 to 18 mmHg. Levels of basic fibroblast growth factor in conditi oned media from microvascular endothelial and retinal pigment epitheli al cell cultures also decreased when the oxygen tension of the medium was reduced from 135 to 18 mmHg. Total transforming-growth-factor beta (and specifically isoforms 1 and 2) in the conditioned media from all three cell types was similarly modulated by oxygen i.e. it decreased as the oxygen tension of the medium was reduced from 135 to 18 mmHg. I n contrast, the steady state messenger RNA levels for both basic fibro blast growth factor and transforming-growth-factor-betal genes in RPE cells increased significantly when the oxygen tension of the medium wa s reduced from 135 to 18 mmHg. These results support the putative role of oxygen in influencing the balance of growth factors during the dev elopment of preretinal new vessels.