Abstract
Abstract: :
Purpose: Newborn rats raised in alternating hyperoxic/hypoxic conditions exhibit abnormal retinal vascular patterns similar to proliferative retinopathy seen in human preterm infants. Rats fed diets deficient in alpha–linolenic acid (ALA) possess low levels of docosahexaenoic acid (DHA), a long–chain polyunsaturated fatty acid that in turn may influence the oxidative state of the developing retina. This study explores interaction of oxygen and DHA as factors in determining severity of vascular pathology in neonatal rats. Methods: Sprague–Dawley dams and litters were fed from embryonic day 16 (E16) to postnatal day 18 (P18) on one of three nutritionally complete diets identical except for fats: 1) ALA–sufficient (soybean oil), 2) ALA–deficient (sunflower oil) or 3) containing 4% lipids as DHA (Martek DHASCO oil). Litters (n=13) were raised in either room air (21% O2) from P0–P18 or in cycling oxygen conditions from P0–P14, then room air to P18. The cycling oxygen condition exposed rats to 50%O2 (50%N2) for 24hr then 10%O2 (90%N2) for 24hr on alternate days. Rats were perfused at P18 with India ink to identify vasculature. Eyes were fixed overnight then wholemounted and imaged. Vascular patterns were quantified and results compared across diets and atmospheric conditions. Results: Rats raised under cycling oxygen conditions matured more slowly, averaged half the size and weight, and were delayed in the extent of retinal vascularization relative to room air rats. Increased vessel tortuosity was seen in all cycling rats relative to room air rats (p<.0001), but diet–related effects were not observed. Analyzing vascular complexity by fractal analysis (skeletonized images; box count method) in higher magnification images (10–20x) showed a trend toward increased density of small vessels from center to periphery in room air rats, but a uniform density in rats raised in cycling conditions. Again, diet–related effects were not observed. Conclusions: DHA content alone neither impairs nor improves oxygen–induced retinopathy rats, supporting use of DHA–supplements for nutritional management of premature human infants. Interaction of oxygen, fatty acids, and other nutritional factors however still may contribute to this form of retinopathy.
Keywords: retinopathy of prematurity • lipids • neovascularization