¡¡¡¡DISCUSSION

¡¡¡¡Many studies indicate that one of the proposed mechanisms for the pathogenesis of ROP includes overproduction of the angiogenic growth factors including VEGF[6,7], resulting invasoconstriction, poor blood flow, and ultimately retinal ischemia. Nutritional factors may play a major role in regulation of these mechanisms. Recent studies of retinal pigment epithelial cells in culture have demonstrated that glutamine deprivation results in a dramatic elevation of VEGF[8].In studies of mammary epithelium, glutamine deprivation increased both VEGF and ILª²8, a potent neutrophil chemoattractant, and these same changes were evident with arginine deprivation[9].In addition, several studies in animals suggest that glutamine supplementation reduces inflammation[10,11]. Premature infants undergoing intensive care are also frequently deprived of both arginine and glutamine[12,13] because of stress. They are unable to maintain endogenous synthesis of these conditionally essential amino acids, making these infants highly vulnerable to glutamine andarginine deprivation. Glutamine and arginine supplementation have both been shown to be safe in lowª²birthª²weight infants[14,15].Recent studies indicated that arginine and glutamine (Argª²Gln) can improve blood flow to the microvasculature via increased local nitric oxide production through the Lª²arginineª²nitric oxide synthase pathway[16,17]. Supplementation of glutamine or arginine has resulted in beneficial effects in human neonates. This study is to demonstrate the beneficial effects of a nutraceutic agent, Argª²Gln dipeptide, in inhibiting retinal angiogenesis. The proposed mechanism is a reduction of VEGF expression in vivo. It may provide a safe way to prevent and treat some forms of proliferative retinopathies including ROP.

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¡¡¡¡12 Neu J. Glutamine supplements in premature infants: why and how. J Pediatr Gastroenterol Nutr2003;37:533ª²535

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¡¡¡¡17 Zhao Y, Ren B, Gao XW. Current research in mechanism and drug therapy of retinopathy of prematurity. Int J Ophthalmol(Guoji Yanke Zazhi)2006;6(6):1382ª²1385

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