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M. B. Grant, L. C. Shaw, N. Sengupta, J. Neu; Combination Arginyl-Glutamine (Arg-Gln) Dipeptide and Docosahexaenoic Acid (DHA) Promote Early Vascular Regrowth Following Hyperoxia Exposure and Reduce Preretinal Neovascularization in the Oxygen-Induced Retinopathy (OIR) Model. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2630.
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Retinopathy of prematurity (ROP) is the major cause of blindness in children. Supplementation with arginine, glutamine or DHA, a major omega-3 fatty acid, results in improved clinical outcomes in premature infants. Previously, we showed that Arg-Gln administered IP inhibits development of abnormal pre-retinal neovascularization in the OIR model (Neu, et al, IOVS, 2006). In this study we examined the protective effect of oral administration of Arg-Gln alone and in combination with DHA in pups undergoing the OIR model.
Nursing dams and pups were returned to normal room air on P12 and gavaged twice daily with: Arg-Gln, DHA, Arg-Gln + DHA or vehicle (P12-P17). Normoxic pups were treated in an identical manner. On P17 the pups were perfused with FITC-labeled dextran. One eye was embedded in paraffin, cross-sectioned and H&E stained for analysis of pre-retinal neovascularization. The retina from the second eye underwent microscopic analysis for measurement of intra-retinal vascular density (P17) (central, mid and peripheral retina) to assess vascular regrowth.
The Arg-Gln dipeptide gave the greatest reduction in pre-retinal neovascularization (65 ± 1%, P < 0.001) compared to DHA (55 ± 2%, P < 0.001) or a combination of both (33 ± 2%, P < 0.001) relative to vehicle. All test compounds dramatically reduced the area of vaso-obliteration assessed in P17 pups (Arg-Gln: 4.8 ± 1.0%, P = 0.03; DHA: 3.6 ± 1.3%, P = 0.04; combination: 5.4 ± 0.7%, P = 0.02) when compared to vehicle (30.4 ± 7.9%). Intra-retinal vascular density was greatest in Arg-Gln groups of pups compared to the other treatment groups.
Treatment with the Arg-Gln dipeptide also was superior to the combination (dipeptide with DHA) or DHA alone, however all treatments dramatically inhibited pre-retinal neovascularization, reduced vaso-obliteration and restored intra- vascular density in the OIR mouse model. These agents may serve as an effective nutraceutics for treatment of ROP.
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