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Silke Becker, Randy Brown, Ashley Brown, Camille Fung, M Elizabeth Hartnett; Analysis of Wnt pathway components during combined intrauterine growth restriction and oxygen-induced retinopathy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3450.
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© ARVO (1962-2015); The Authors (2016-present)
Poor postnatal growth has been linked to retinopathy of prematurity (ROP). Wnt signaling is important in development, and genetic variants of members of the Wnt pathway have been associated with increased severity of ROP. We addressed the hypothesis that poor postnatal growth interferes with expression of Wnt pathway components in the retina in association with increased ROP severity by using a model of oxygen-induced retinopathy (OIR) in growth restricted mouse pups.
C57BL/6J mice were implanted on embryonic day 12.5 with micro-osmotic pumps containing vehicle (0.5% ethanol, control) or the thromboxane A2 analogue U46619 (in 0.5% ethanol, Txa) to induce maternal gestational hypertension. Litters in OIR were exposed to 75% oxygen from postnatal day (p)7 for 5 days and returned to room air (RA) for 5 days. Control litters were raised in RA until p17. Avascular retina/total retinal area (AVA) and intravitreal neovascular/total retinal area (IVNV) were determined in lectin-stained retinal flat mounts. Whole retinas were analyzed for VEGF, Wnt7a, Wnt10a, Dvl1, Fzl4 and Fzl7 mRNA by qPCR and normalized to the housekeeping gene TATA-binding protein. Data were expressed as means ± SEM, with 7-8 pups per group. Statistical significance was determined by t-test or one way ANOVA.
Mean birth weight was reduced in pups born to Txa-treated dams (1.19±0.02g, n=21) compared to control dams (1.30±0.00g, n=28, P<0.001). At p17, body weight was greater in Txa/OIR (7.59±0.20g, n=7) compared to control/OIR pups (6.79±0.11g, n=8, P<0.05). There was no difference between AVA or IVNV in Txa/OIR vs. control/OIR pups. VEGF mRNA in retinal lysates was increased in both control and Txa pups in OIR compared to RA (control/OIR 1.36±0.07, n=7 vs. control/RA 1.02±0.07, n=8, P<0.01; Txa/OIR 1.36±0.08, n=7 vs. Txa/RA 1.09±0.05, n=8, P<0.05), but not altered by Txa compared to vehicle control. Wnt7a, Wnt10a, Dvl1, Fzl4 and Fzl7 mRNA in pup retinas were not different in Txa/OIR compared to control/OIR pups.
Neither AVA nor IVNV was different in Txa compared to control pups in OIR at postnatal day 17. Although VEGF was upregulated by OIR, no differences in VEGF were observed between Txa and control pups in OIR. No difference was noted in mRNA expression of several Wnt pathway components at p17 in this model, but analysis of other time points will be considered in future studies.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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