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M. Coassin, K. G. Duncan, K. R. Bailey, D. M. Schwartz; Hypothermia Reduces the Release of Vascular Endothelial Growth Factor by Cultured Retinal Pigment Epithelium. Invest. Ophthalmol. Vis. Sci. 2008;49(13):859.
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Vascular endothelial growth factor (VEGF) is a critical regulator of retinal angiogenesis in exudative age related macular degeneration (AMD). We hypothesized that the release of VEGF by the retinal pigment epithelium (RPE) might be reduced by hypothermia through a reduction of cellular metabolism. To demonstrate this correlation, we studied the effect of temperature on the cultured RPE VEGF secretion. Then, we investigated the effect of hypothermia on VEGF expression by RPE cells in normoxic versus hypoxic conditions.
To determine temperature effects on VEGF secretion, RPE cells were cultured for 96 hours at 32.5, 34, 37 and 40 °C in normoxic conditions (5% CO2 and 20% O2). The levels of VEGF were measured using a commercial ELISA kit. The metabolic activity of RPE cells was assessed with the Vybrant Cell Metabolic Assay Kit.To determine effects of hypothermia on VEGF secretion under hypoxic conditions, four groups of RPE cells were incubated for 96 hours under the following conditions: 37°C and 20% O2; 32.5°C and 20% O2; 37°C and 1% O2; and, at 32.5°C and 1% O2. The levels of VEGF were then measured using the ELISA assay.
Hypothermia decreases both VEGF secretion and cellular metabolism of cultured RPE cells compared to physiologic temperature. Furthermore, the effect of hypoxia on increasing VEGF secretion by these cells is mitigated by hypothermia. Specifically, a 4.5° C reduction in temperature reduced RPE VEGF secretion under hypoxic conditions to similar levels observed under normoxic conditions at 37° C.
Moderate hypothermia may induce an almost physiologic release of VEGF by RPE, even under hypoxic conditions. Hypothermia might protect the outer retina and reduce the neovascular stimulus in patients with AMD. Effects of chronic cooling on visual function and its potential ocular toxicity need further study.
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