Renin-Angiotensin System in Proliferative Diabetic Retinopathy and Its Gene Expression in Cultured Human Mu¨ller Cells

Purpose: To determine if the renin-angiotensin system (RAS) is involved in diabetic retinopathy, we measured the levels of angiotensin-converting enzyme (ACE) and angiotensin II in the vitreous of patients with proliferative diabetic retinopathy (PDR). We also investigated whether the genes of the RAS factors were expressed by cultured human Mu¨ller cells. Methods: Vitreous samples were collected during vitreous surgery from patients with PDR, and from patients with idiopathic macular hole, who served as controls. The concentration of ACE was analyzed, and the level of angiotensin II was quantitatively determined by double antibody radioimmunoassay. In addition, the cDNA, prepared from the mRNA extracted from cultured human Mu¨ller cells, was used as a template for reverse transcriptase-polymerase chain reaction with primers selected for renin, angiotensinogen, ACE, and angiotensin receptor type I. Results: The mean concentration of ACE was 0.82 ± 0.73 IU/L at 37°C in the PDR group, which was significantly higher than the 0.05 ± 0.07 IU/L at 37°C in the controls. The mean concentration of angiotensin II was 8.77 ± 4.57 pg/mL in the PDR group, which was significantly higher than the 5.1 ± 1.7 pg/mL in the controls. mRNA for renin, angiotensinogen, ACE, and angiotensin receptor type I was detected in cultured human Mu¨ller cells. Conclusions: The RAS is locally activated in eyes with PDR, and Mu¨ller cells may play a role in this local activation.