Renin-angiotensin system in proliferative diabetic retinopathy and its gene expression in cultured human müller cells.
OBJECTIVE
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 Müller 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 Müller 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 degrees C in the PDR group, which was significantly higher than the 0.05 +/- 0.07 IU/L at 37 degrees 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 Müller cells.


CONCLUSIONS
The RAS is locally activated in eyes with PDR, and Müller cells may play a role in this local activation.
Kida
Teruyo
T
Department of Ophthalmology, Osaka Medical College, Osaka, Japan.
Ikeda
Tsunehiko
T
Nishimura
Masato
M
Sugiyama
Tetsuya
T
Imamura
Yutaka
Y
Sotozono
Chie
C
Nishida
Kohji
K
Kinoshita
Shigeru
S
Yoshimura
Manabu
M
Nakamura
Kimitoshi
K
Inokuchi
Naoki
N
D000804:Angiotensin II / Q000378:metabolism; D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003239:Connective Tissue Cells / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism; D012083:Renin / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014822:Vitreous Body / Q000378:metabolism
D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D012083:Renin