Abstract
Purpose:
Most vision impairment after perinatal hypoxia-ischemia (periHI) is thought to be due to cortical damage. However, retinal blood supply is also impaired, and data from animal models suggests retinal damage. Here, we examined two main issues in development and function of the visual system in a model of periHI: 1) whether optokinetic head-tracking (OKT)—a head-turn behavior to drifting gratings that depends on subcortical retinal input but does not require the visual cortex—is impaired, and 2) whether function of the output neurons of the retina, the retinal ganglion cells (RGCs), is altered.
Methods:
We performed unilateral carotid cauterization (“ipsi-side” vs. opposite “contra-side”) followed by 8% oxygen for 2 hrs on postnatal day (P)2 and P7 Long-Evans outbred rats (Harlan). In OKT behavior, each direction is independently driven by one eye, unaffected by loss of input from the other eye. OKT thresholds of contrast (at 0.103 cyc/deg, “CT”) and spatial frequency (at max. contrast, “SPFT”) were determined at P30-35 for both horizontal directions. RGC parameters were determined using a multi-electrode array to record extracellular light-evoked spiking at P30-35. ON and OFF RGC receptive fields (RFs) were mapped using white-noise checkerboards. Latency was the position of the main peak of the temporal linear filter. A light square covering the array was varied sinusoidally at 18 contrasts ranging from 2.4% to 92% and presented at 3.75 Hz to find RGC CT. Next, 10 frequencies from 0.75 Hz to 12.5 Hz at 50% contrast were used to find RGC optimal frequency.
Results:
For P2 and P7 surgeries, both SPFT and CT were worse for the ipsi-side compared to controls. For the contra-side, only CT was worse; SPFT was unaffected. The P2 group was more impaired than the P7 group only for ipsi-side SPFT. For both the P2 and P7 groups, SPFT but not CT was significantly worse for the ipsi-side compared to the contra-side of the same rats. In the P7 surgery group, ON but not OFF RGC latencies were longer than in controls. RF diameters were unchanged, and preliminary evidence indicates contrast thresholds and optimal frequencies were also unchanged.
Conclusions:
Because ON RGC latency and subcortical OKT were impaired, periHI may damage retinal circuits and possibly the accessory optic nuclei. The accessibility of the eye may offer new treatment opportunities to preserve vision in periHI patients.
Keywords: 688 retina •
548 hypoxia •
531 ganglion cells