HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Neu, J. Articles by Grant, M. B. Search for Related Content PubMed PubMed Citation Articles by Neu, J. Articles by Grant, M. B.

The Dipeptide Arg-Gln Inhibits Retinal Neovascularization in the Mouse Model of Oxygen-Induced Retinopathy

²From the Departments of Pharmacology and Therapeutics, and ¹Pediatrics, University of Florida, Gainesville, Florida.

PURPOSE. Premature infants undergoing intensive care are highly vulnerable to amino acid deprivation. Supplementation of glutamine or arginine has resulted in beneficial effects in human neonates. This study was conducted to examine the effect of the dipeptide arginyl-glutamine (Arg-Gln) on vascular endothelial cell growth factor (VEGF) levels in primary human retinal pigment epithelial (hRPE) cell cultures and on inhibition of neovascularization in the oxygen-induced retinopathy (OIR) model.

METHODS. The effects of Arg-Gln on VEGF levels were measured in supernates from hRPE cells by using ELISAs. For in vivo studies, mouse pups received twice-daily intraperitoneal injections of Arg-Gln, a control dipeptide (Ala-Gly) or were not injected. Retinal flatmounts from one cohort were prepared and retinal vessel morphology examined. The contralateral eyes were embedded, sectioned, and stained to count preretinal neovascular nuclei. RNA was isolated from retinas of selected animals and was used to quantify VEGF mRNA by real-time RT-PCR.

RESULTS. Treatment of hRPE cells with Arg-Gln decreased VEGF levels in a dose-dependent manner. In the OIR model, Arg-Gln at 5 g/kg per day reduced preretinal neovascularization by 82% ± 7% (P < 0.005), when compared with the control dipeptide Ala-Gly, and reduced VEGF mRNA by 64% ± 9% (P < 0.001).

CONCLUSIONS. Arg-Gln dramatically inhibited retinal neovascularization in the OIR model. This effect was associated with a reduction in retinal VEGF mRNA levels. Similarly the dipeptide reduced VEGF expression in hRPE cells, a cell type likely to respond to retinal hypoxia by expressing VEGF. Arg-Gln appears to be safe and, with future studies in human infants, may prove beneficial in the prevention of ROP.

This article has been cited by other articles:

				T. S. Raghuveer and J. M. Belmont Human Milk Intake and Retinopathy of Prematurity in Extremely Low Birth Weight Infants Pediatrics, September 1, 2008; 122(3): 686 - 687. [Full Text] [PDF]

				Y. Saito, A. Uppal, G. Byfield, S. Budd, and M. E. Hartnett Activated NAD(P)H Oxidase from Supplemental Oxygen Induces Neovascularization Independent of VEGF in Retinopathy of Prematurity Model Invest. Ophthalmol. Vis. Sci., April 1, 2008; 49(4): 1591 - 1598. [Abstract] [Full Text] [PDF]