Abstract
Purpose :
Cortical/cerebral visual impairment (CVI) is an unmet clinical need and our poor understanding of the neural correlates for this visual disorder limits treatment options. CVI is the leading cause of congenital visual impairment in children in the United States and accounts for about one quarter of all cases for ages one to three. CVI is most often caused by hypoxic perinatal injury to central visual pathways and encompasses deficits in spatial vision, attention, and object recognition. There is no animal model of CVI that captures even a subset of the deficits in vision. We hypothesize that mice treated with early postnatal hypoxia will display disruptions in neural circuity that underlie aspects of visual behavior and will serve as a model of CVI.
Methods :
Here, we have developed a murine early postnatal hypoxic model of CVI by exposing mice to 9.5% O2 at postnatal day (P) 3 for 7, 14, or 30 days. As adults (>P40), we first test their motor function with the rotarod, visual acuity with the visual water task, and binocular depth perception with the pole descent task. Next, we use anterograde tracing of retinal afferents to study the pattern of eye specific terminations in the dorsal lateral geniculate nucleus (dLGN), the exclusive relay of retinal information in route to visual cortex.
Results :
In hypoxic mice, motor performance was normal and indistinguishable from normoxic mice. However, average visual acuity was reduced, and the range of acuity broader for groups of mice receiving early postnatal hypoxia for 7, 14, or 30 days. Binocular depth perception was also impaired for each hypoxia group relative to normoxic controls. The pattern of eye specific segregation in dLGN was disrupted, with hypoxic mice showing a higher degree of overlap between ipsilateral and contralateral projections.
Conclusions :
Mice receiving early postnatal hypoxia have normal motor performance, but impaired visually guided behavior. These mice also display a pattern of immature retinogeniculate projections, similar to overlapping projections seen during early postnatal development. These visual deficits resemble facets of human CVI. Disruption in retinogeniculate axon segregation suggests, in addition to cortex, thalamus may be implicated in CVI. The establishment of a hypoxic mouse model of CVI is vital to progress in understanding the disorder and developing rational treatment options.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.