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Yves Sauve, Stephane Bourque, Sharee Kuny, Sandra Davidge; Intrauterine growth restriction is associated with long-term retinal dysfunction in rats. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3271.
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Prenatal stressors such as hypoxia can alter growth trajectory and induce phenotypic changes in the fetus, which increase its predisposition to age-related complications. Here, we tested the hypothesis that aged offspring exposed to prenatal hypoxia during their last week of gestation would exhibit exacerbated age-related functional decline of the retina.
Female Sprague-Dawley rats (maintained at 11.5% O2 from gestational day GD15 to GD21, term=GD22 to induce intra-uterine growth restriction, IUGR) and normoxic controls (maintained at 21% O2 throughout pregnancy) had retinal function assessed at 2 and 14 months of age with electroretinogram (ERG) recordings. Retinal anatomy was also assessed at similar ages.
Dark-adapted mixed a-wave (rod and cone activity) and b-wave (bipolar cell activity) amplitudes were diminished in IUGR versus normoxic offspring; these effects were most apparent at 14 months. Young and aged IUGR offspring also had lower mixed a-wave thresholds, and mixed b-wave response amplitudes were markedly reduced under light adaptation. Light-adapted oscillatory potential peak amplitudes were also lower in IUGR offspring at both 2 and 14 months. Light-adapted flicker fusion frequency was also reduced in aged IUGR versus age-matched normoxic offspring. There was no evidence of photoreceptor loss in either young or aged IUGR offspring when compared to age-matched controls as evidenced with immunofluorescence confocal microscopy. However, we detected elevated levels of glial fibrillary acidic protein (GFAP) accumulation, supporting likely retinal stress.
Conclusion: Early stressors are known to impact various aspects of neural function, including sensory systems. Here, we report that adult offspring born at term but exposed to prenatal hypoxia during their last week of gestation exhibited alterations in retinal function, characterized by (1) age related rod dysfunction, and (2) specific early non-progressive dysfunction specific to the cone system reflected by differences in flicker fusion frequency and peak amplitudes in oscillatory potential in IUGR offspring. These changes occurred without anatomical losses in the rods and cones.
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