Increased expression of angiotensin-converting enzyme in retinas of diabetic rats.
OBJECTIVE
The aim of this study was to examine the localization and the changes in the amount of angiotensin-converting enzyme (ACE) and the relationship between the renin-angiotensin (RA) system and vascular endothelial growth factor (VEGF)/VEGF-receptor system in the retinas of diabetic rats.


METHODS
Immunohistochemical localization of ACE, VEGF, and VEGF-receptor fetal liver kinase-1 (Flk-1) was examined in cryosections of the retinas of streptozotocin-injected diabetic rats. A semi-quantitative comparison of diabetic rats with age-matched controls was also performed by counting the ACE- or Flk-1-positive vessels per microscopic field.


RESULTS
ACE immunoreactivity was localized in the retinal vessel walls, and the percentages of ACE-positive vessels were significantly increased in the retinas of diabetic rats maintained 3 to 5 months. Both VEGF and Flk-1 signals increased simultaneously with the increment of ACE immunoreactivity.


CONCLUSIONS
ACE, expressed in the retinal vessel walls, increases simultaneously with the increment of both VEGF and Flk-1 in the retinas of diabetic rats, suggesting that upregulation of ACE might play some role in the progression of diabetic retinopathy through the VEGF/VEGF receptor system.
Okada
Y
Y
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yamanaka
I
I
Sakamoto
T
T
Hata
Y
Y
Sassa
Y
Y
Yoshikawa
H
H
Fujisawa
K
K
Ishibashi
T
T
Inomata
H
H
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000473:pathology; D003930:Diabetic Retinopathy / Q000201:enzymology* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008222:Lymphokines / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D012084:Renin-Angiotensin System / Q000502:physiology; D012171:Retinal Vessels / Q000201:enzymology* / Q000473:pathology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D007703:Peptidyl-Dipeptidase A