Abstract
Premature infants with retinopathy of prematurity (ROP) have neovascularization of the retina, potentially resulting in low vision and even blindness. Some of these infants still have visual impairment, even if ROP resolves as they age. However, the mechanisms underlying the visual problems post-ROP are poorly understood. Because the pathological neovascularization in ROP infants can be mimicked in a mouse model with oxygen-induced retinopathy (OIR), we recapitulated post-ROP with post-OIR mice a few months after spontaneous regression of retinal neovascularization. Our pattern electroretinogram test demonstrates that post-OIR mice exhibit reduced P1-N2 responses, suggesting the impairment of retinal ganglion cells, the retina's output neurons. However, immunohistochemistry reveals that the density of retinal ganglion cells remains unchanged in post-OIR mice, indicating that the aforementioned pattern electroretinogram changes are functional. Our data further demonstrate that both light-adapted ex vivo electroretinogram a-waves (cone responses) and in vivo electroretinogram b-waves (ON cone bipolar cell responses) were significantly impaired in post-OIR mice. These results suggest that post-OIR impairment of the retinal cone pathway appears to result in the dysfunction of retinal ganglion cells, contributing to visual problems. A similar cellular mechanism could occur in post-ROP children, which is responsible for their visual impairment.