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Suna Jung, Anna Polosa, Pierre Lachapelle, Pia Wintermark; Neonatal Hypoxia-Ischemia Retinopathy: Severity at Onset Determines Fate. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5077.
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Neonatal Hypoxia-Ischemia (HI) can cause brain injury and blindness in human infants. The Vannucci model (unilateral ligation of the common carotid artery followed by a period of hypoxia) is widely used to study the brain injury resulting from HI and we have previously shown, in 60-day-old rats, evidence of a concomitant retinopathy. The purpose of this study was to investigate if the HI retinopathy is of the destructive or degenerative type.
10-day-old male Long-Evans rat pups received left common carotid artery ligation followed by 2-hour hypoxia (8% oxygen) (N=17). Control pups (N=8) received sham surgery. Electroretinograms (ERGs) were obtained at P17, P22, P30 and P60 from the left eye. Eyes were subsequently collected for retinal histology (P60).
HI animals were divided into mild (N=6), moderate (N=5) and severe (N=6) subgroups based on the ERG b-wave amplitude (at P17) compared to normal. In control the ERG showed an increase in amplitude from P17 through P22 (scotopic a- and photopic b-waves) or P30 (scotopic b-wave). The scotopic a-wave was only affected in severe HI (20% amplitude attenuation) and peak of maturation delayed to P30. The scotopic and photopic b-wave amplitudes were attenuated at P17 (scotopic: by 37%, 54%, 100%; photopic: by 28%, 78%, 99%; mild, moderate, severe HI, respectively). The mild HI group showed a gradual increase in the b-wave amplitudes such that they were not significantly different from control at P60. The moderate and severe HI also showed increasing trend of the b-wave amplitudes over time but only marginally. Histology at P60 revealed intact photoreceptor outer nuclear layer but damaged inner retinal layers at varying degrees, providing structure-function correlation.
Our data suggest that neonatal HI causes a retinopathy that spares photoreceptors but manifests, to various extents, in the inner retina from early on following the insult. A lack of further functional attenuation over time suggests that the pathology is destructive. Interestingly, there was an evidence of functional recovery with maturation especially in the mild HI group that assumed normal ERG function at P60. These findings are in parallel with variable degree of brain injury seen in infants that suffered neonatal HI, and suggest the possibility that they might experience a retinal injury as well. Consequently, retinal function should be monitored regularly.
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