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Updated: May 14, 2025
Oxygen-Induced Retinopathy Model for Ischemic Retinal Diseases in Rodents
Published on: September 16, 2020
Long-Term Impairment of Retinal Ganglion Cell Function After Oxygen-Induced Retinopathy
Adam M Schmitz1, Stephanie M Bumbaru1, Laith S Fakhouri1
1Eye Research Institute, Oakland University, Rochester, MI 48309, USA.
Insights
Retinopathy of prematurity (ROP) can cause lasting vision problems in premature infants. A mouse model shows that cone pathway dysfunction, not cell loss, leads to retinal ganglion cell impairment after ROP regression.
Area of Science:
- Ophthalmology
- Neuroscience
- Developmental Biology
Background:
- Retinopathy of prematurity (ROP) is a leading cause of childhood blindness.
- Visual impairment can persist in children even after ROP resolves.
- The underlying mechanisms of post-ROP visual deficits are not well understood.
Purpose of the Study:
- To investigate the functional and cellular changes in the retina after the regression of neovascularization.
- To elucidate the mechanisms contributing to visual impairment in a mouse model mimicking post-ROP conditions.
Main Methods:
- Oxygen-induced retinopathy (OIR) mouse model to mimic ROP.
- Pattern electroretinography (pERG) to assess retinal ganglion cell function.
- Immunohistochemistry to evaluate retinal ganglion cell density.
- Ex vivo and in vivo electroretinography (ERG) to analyze cone and bipolar cell function.
Main Results:
- Post-OIR mice showed reduced pERG P1-N2 responses, indicating functional impairment of retinal ganglion cells.
- Retinal ganglion cell density remained unchanged, suggesting functional rather than structural deficits.
- Significant impairment of light-adapted ERG a-waves (cone responses) and b-waves (ON cone bipolar cell responses) was observed.
Conclusions:
- Post-OIR retinal impairment stems from cone pathway dysfunction, leading to retinal ganglion cell dysfunction.
- This functional deficit in the cone pathway contributes to visual problems in the post-OIR model.
- Similar mechanisms may underlie visual impairment in children with resolved ROP.
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.
