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PMID: 12937129 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Retinal angiogenesis is mediated by an interaction between the angiotensin type 2 receptor, VEGF, and angiopoietin.

The American journal of pathology ·Vol. 163 ·No. 3 ·2003-09-00 ·Pages 879-87

Sarlos S, Rizkalla B, Moravski CJ, Cao Z, Cooper ME, Wilkinson-Berka JL

Abstract

There is evidence that angiotensin II, vascular endothelial growth factor (VEGF), angiopoietins, and their cognate receptors participate in retinal angiogenesis. We investigated whether angiotensin type 2-receptor blockade (AT2-RB) reduces retinal angiogenesis and alters the expression of VEGF/VEGF-R2 and angiopoietin-Tie2. Retinopathy of prematurity (ROP) was induced in Sprague Dawley (SD) rats by exposure to 80% oxygen from postnatal (P) days 0 to 11, followed by 7 days in room air. ROP shams were in room air from P0-18. A group of ROP rats received the AT2-RB, PD123319, by mini-osmotic pump (5 mg/kg/day) from P11-18 (angiogenesis period). Evaluation of the retinal status of the AT2 receptor indicated that this receptor, as assessed by real-time PCR, immunohistochemistry, and in vitro autoradiography, was present in the retina, was more abundant than the AT1 receptor in the neonatal retina, and was increased in the ROP model. AT2-RB reduced retinal angiogenesis. VEGF and VEGF-R2 mRNA were increased in ROP and localized to blood vessels, ganglion cells, and the inner nuclear layer, and were decreased by PD123319. Angiopoietin2 and Tie2, but not angiopoietin1 mRNA were increased with ROP, and angiopoietin2 was reduced with PD123319. This study has identified a potential retinoprotective role for AT2-RB possibly mediated via interactions with VEGF- and angiopoietin-dependent pathways.

MeSH Terms
Aging/metabolism Angiogenesis Inducing Agents/metabolism Angiopoietin-2 Animals Animals, Newborn Autoradiography Computer Systems Endothelial Growth Factors/genetics,metabolism Immunohistochemistry In Situ Hybridization Intercellular Signaling Peptides and Proteins/genetics,metabolism Lymphokines/genetics,metabolism Neovascularization, Pathologic/pathology,physiopathology Oxygen Polymerase Chain Reaction RNA, Messenger/metabolism Rats Rats, Sprague-Dawley Receptor, Angiotensin, Type 1 Receptor, Angiotensin, Type 2 Receptors, Angiotensin/metabolism Retina/metabolism Retinal Diseases/chemically induced,pathology,physiopathology Retinal Vessels/pathology,physiopathology Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor Receptor-2/genetics Vascular Endothelial Growth Factors
Chemicals
Angiogenesis Inducing Agents Angiopoietin-2 Endothelial Growth Factors Intercellular Signaling Peptides and Proteins Lymphokines RNA, Messenger Receptor, Angiotensin, Type 1 Receptor, Angiotensin, Type 2 Receptors, Angiotensin Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Vascular Endothelial Growth Factor Receptor-2 Oxygen
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Sarlos Stella
Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.
Rizkalla Bishoy
Moravski Christina J
Cao Zemin
Cooper Mark E
Wilkinson-Berka Jennifer L
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)63448-7
Published
2003-09-00
Pages
879-87
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1868261
Subset
IM
External Links
PubMed source DOI: 10.1016/S0002-9440(10)63448-7 PMC Full Text View journal details
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