Abstract | Purpose: Methods: Postnatal day 7 (P7) pups were maintained at 75% oxygen for 5 days and then returned to room air on P12. Pups were gavaged twice daily with Arg-Gln or vehicle from P12 to P17 and eyes were harvested for analysis on P17. Vaso-obliteration and vascular density were assessed on retinal flat mounts and preretinal neovascularization was assessed on retinal cross sections. Retinas were used for measurement of DHA and 10,17S-docosatriene ( neuroprotectin D1, NPD1), a key DHA-derived lipid, and for analysis by reverse-phase protein array (RPPA). Results: With Arg-Gln treatment, retinal DHA and NPD1 levels were increased in OIR pups. Arg-Gln reduced preretinal neovascularization by 39 ± 6% (P < 0.05) relative to vehicle control. This was accompanied by a restoration of vascular density of the retina in the pups treated with Arg-Gln (73.0 ± 3.0%) compared to vehicle (53.1 ± 3.4%; P < 0.05). Arg-Gln dipeptide restored OIR-induced signaling changes toward normoxia and was associated with normalization of insulin-like growth factor receptor 1 signaling and reduction of apoptosis and an increase in anti-apoptosis proteins. Conclusions:
Arg-Gln may serve as a safer and easily tolerated nutraceutical agent for prevention or treatment of ROP.
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Authors | Lynn Calvin Shaw, Sergio Li Calzi, Nan Li, Leni Moldovan, Nilanjana Sengupta-Caballero, Judith Lindsey Quigley, Mircea Ivan, Bokkyoo Jun, Nicolas G Bazan, Michael Edwin Boulton, Julia Busik, Josef Neu, Maria B Grant |
Journal | Investigative ophthalmology & visual science
(Invest Ophthalmol Vis Sci)
Vol. 59
Issue 2
Pg. 858-869
(02 01 2018)
ISSN: 1552-5783 [Electronic] United States |
PMID | 29490339
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Dipeptides
- arginyl-glutamine
- protectin D1
- Docosahexaenoic Acids
- Oxygen
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Topics |
- Administration, Oral
- Animals
- Animals, Newborn
- Chromatography, High Pressure Liquid
- Dipeptides
(administration & dosage)
- Disease Models, Animal
- Docosahexaenoic Acids
(metabolism)
- Female
- Male
- Mice
- Mice, Inbred C57BL
- Oxygen
(toxicity)
- Pregnancy
- Retina
(metabolism)
- Retinal Neovascularization
(chemically induced, metabolism, prevention & control)
- Retinal Vessels
(drug effects, pathology)
- Retinopathy of Prematurity
(chemically induced, metabolism, prevention & control)
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