The natriuretic peptide system (A-, B- and C-type) has a powerful effect on systemic blood circulation (natriuresis, diuresis ans plasma shift) causing haemoconcentration causing increased oxygen carrying capapcity of blood. A high concentration of a member of the natriuretic peptide family has been found from the vitreous of patients suffering of proliferative diabetic retinopathy (PDR). The stimulus to which the natriuretic peptide system responded in PDR, however, has remained unknown. We tested the hypothesis that hypoxic conditions will increase the release of BNP (B-type of natriuretic peptides) from human retinal pigment epithelium (RPE) cell cultureMethods
Human retinal pigment epithelium cells (ARPE-19) were exposed to hypoxia for 2h, 4h, 6h, 8h and 24h. The amount of BNP and VEGF (positive control) were measured at different time points in culture media using EIA. Hypoxia-Inducible Factor (HIF), a protein, which is the master switch in regulating all the responses to hypoxia downstream, was measured using Western blotting.Results
At 24h, the amount of BNP in culture media was significantly higher in hypoxic than in normoxic conditions. Also, the concentration of both VEGF and HIF were significantly higher in hypoxia.Conclusion
Hypoxia increases the release of BNP from RPE cells and the response is mediated by HIF.The present results characterize for the first time a stimulus for the natriuretic peptide system in human retina and explain previous clinical findings. Thus, the measurement of natriuretic peptides in the vitreous may guide the treatment of the intraocular diseases in which the retina is suffering from hypoxia. Future perspectives: Natriuretic peptides regulate oxygen transport in all tissues?