The retina expresses a local renin-angiotensin system (RAS). This study aimed to investigate the influence of systemic modulation of renin synthesis on the expression of renin in the retinal pigment epithelium (RPE), which forms part of the blood/retina barrier. Freshly isolated RPE cells showed expression of renin 1A, which is the secreted isoform of renin. Systemic administration of the angiotensin-converting enzyme inhibitor enalapril in mice increased the renin expression in both the kidney and the retina. Systemic infusion of ANG II led to a decrease in the renin expression in the kidney and in the retina and RPE. The ANG II-dependent down-regulation of renin expression in the RPE was prevented by systemic application of the AT(1) receptor blocker losartan. However, water deprivation lead to an increase of the renin expression in the kidney but unexpectedly to a decrease of the renin expression in the retina. In sections of the mouse retina, the ANG II receptor AT(1) was found in the RPE and localized at the blood side of the epithelium. Short-time cultured RPE cells showed increases in intracellular free Ca(2+) in response to stimulation by ANG II that were sensitive to losartan. In summary, we conclude that the renin expression in cells of the blood/retina barrier is influenced by the systemic RAS. ANG II circulating in the plasma is likely a mediator of this influence.