Retinal neovascularization is prevented by blockade of the renin-angiotensin system.
Both angiotensin II and vascular endothelial growth factor are angiogenic agents that have recently been implicated in the pathogenesis of proliferative diabetic retinopathy. In this study, retinal neovascularization was examined in a model of retinopathy of prematurity with the use of neonatal transgenic (mRen-2)27 rats, which overexpress renin in tissues, and Sprague-Dawley rats. Blockers of the renin-angiotensin system were administered during the neovascularization period. The ACE inhibitor lisinopril and the angiotensin type 1 receptor antagonist losartan both increased retinal renin levels and prevented inner retinal blood vessel growth. Quantitative in situ hybridization revealed that the expression of vascular endothelial growth factor and its type 2 receptor in the inner retina and proliferating blood vessels were increased in rats with retinopathy of prematurity. Lisinopril reduced both retinal vascular endothelial growth factor and its type 2 receptor mRNA in retinopathy of prematurity rats, whereas losartan had no effect. It is predicted that agents that interrupt the renin-angiotensin system may play an important role as retinoprotective agents in various forms of proliferative retinopathy.
Moravski
C J
CJ
Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia.
Kelly
D J
DJ
Cooper
M E
ME
Gilbert
R E
RE
Bertram
J F
JF
Shahinfar
S
S
Skinner
S L
SL
Wilkinson-Berka
J L
JL
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000502:physiology; D006801:Humans; D017403:In Situ Hybridization; D007231:Infant, Newborn; D017706:Lisinopril / Q000494:pharmacology; D008222:Lymphokines / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D012160:Retina / Q000378:metabolism; D015861:Retinal Neovascularization / Q000378:metabolism / Q000517:prevention & control*; D012178:Retinopathy of Prematurity / Q000473:pathology / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D017706:Lisinopril; D012083:Renin