Abstract
Purpose:
Hypoxic-ischemic encephalopathy (HIE) is a brain injury caused by oxygen and blood flow deprivation that may lead to neurodevelopmental delay in neonates. Brain and eye abnormalities are often associated, and retinal abnormalities have been identified in HIE rats. Given the versatility of genetic manipulation and therapies available with a mouse model, we sought to determine whether there are visual consequences of HIE as evidenced by electroretinography in mice.
Methods:
Postnatal day 9 C57/BL6 mice were subjected to Vannucci’s neonatal HIE model by left common carotid artery cauterization and exposure to 10% O2 at 37°C for 50 min. Sham operated mice had skin incision and manipulation of the left common carotid artery without hypoxia. ERGs were performed on 6 wk old HIE and sham mice using the HMsERG system (Ocuscience, Kansas) under Ketamine (90), Xylazine (7.5), and acepromazine (1.75) mg/kg mixed anesthesia IP. Scotopic ERGs were performed at half-log unit intervals from an intensity of 0.03 to 30 log cd-s/m2. Amplitudes and implicit times for both the a- and b-waves were measured and averaged. Oscillatory Potentials (OP) were extracted by filtering the ERG response at 300 Hz to determine inner retinal integrity. The mice were both age and sex-matched. The student t-test was used for statistical comparison and a value of p < 0.05 was deemed significant.
Results:
No significant differences were noted in the a-wave amplitude at a flash intensity of 3 log cd-s/m2 between the two eyes in the HIE injured mice. For the sham injured mice, the a-wave amplitudes were also comparable. In contrast, the ERG b-wave amplitude was severely affected in the HIE mouse eye on the side of the carotid manipulation (210.8 ± 32.9) as compared to the contralateral control eye (447.2 ± 31.3; p < 0.005). OP1 and OP2 waveforms were also severely reduced (OP1 33 vs. 76 uV, P<0.01; OP2 40 vs. 97 uV, P<.005). There was no difference between the two eyes in the sham-treated animals for the a-wave, b-wave or OP amplitudes.
Conclusions:
HIE is associated with visual deficits in the mouse as determined by electroretinography, with the a-wave amplitude spared as compared to significant changes in the b-wave. We also demonstrate the novel observation of reduction in the OP1 and OP2 amplitudes. We suggest that the ERG may be a useful tool to monitor attempts to rescue encephalopathy with novel approaches to therapy in a non-invasive and longitudinal fashion.