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Updated: Dec 24, 2025
Monitoring Dynamic Growth of Retinal Vessels in Oxygen-Induced Retinopathy Mouse Model
Published on: April 2, 2021
Long-term evaluation of retinal morphology and function in a mouse model of oxygen-induced retinopathy
Olachi J Mezu-Ndubuisi1,2, Erica L Macke3, Raja Kalavacherla1
1Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI.
Insights
High oxygen levels in premature infants can cause retinopathy of prematurity (ROP), leading to vision loss. This study shows persistent retinal damage and dysfunction in a mouse model, highlighting the need for new therapies to preserve sight.
Area of Science:
- Ophthalmology
- Neonatal care
- Retinal vascular biology
Background:
- Retinopathy of prematurity (ROP) results from abnormal retinal vascularization due to high oxygen exposure in premature infants.
- Existing therapies for ROP may not fully restore visual function, leaving functional deficits.
- Long-term consequences of ROP on retinal structure and function require further investigation.
Purpose of the Study:
- To investigate the long-term effects of hyperoxia on retinal morphology and function.
- To utilize a mouse model of oxygen-induced ischemic retinopathy (OIR) to study ROP.
- To assess persistent functional deficits and structural abnormalities in OIR.
Main Methods:
- Oxygen-induced ischemic retinopathy (OIR) model in mice (77% oxygen exposure).
- In vivo assessments: fluorescein angiography (FA), spectral-domain optical coherence tomography (SD-OCT), focal electroretinography (fERG).
- Histological analyses: retinal morphology, gliosis, microglia activation, apoptosis, and synaptic structure.
Main Results:
- OIR mice exhibited capillary attrition and inner retinal thinning.
- fERG revealed both outer and inner retinal dysfunction.
- Histology confirmed disorganized retinal structure, increased gliosis, microglial activation, apoptosis, and ectopic synapses with age.
Conclusions:
- Persistent histological abnormalities, including ectopic synapses and apoptosis, correlate with long-term in vivo retinal dysfunction in OIR.
- These findings in the OIR mouse model provide insights into ROP pathogenesis.
- Further research into the mechanisms of persistent phenotypes may reveal novel therapeutic targets for ROP.
Purpose:
Retinopathy of prematurity (ROP) is a condition of aberrant retinal vascularization in premature infants in response to high levels of oxygen used for critical care that can potentially cause blindness. Although therapies to mitigate vascular abnormalities are being evaluated, functional deficits often remain in patients with treated or regressed ROP. This study investigated long-term outcomes of hyperoxia on retinal morphology and function using a mouse model of oxygen-induced ischemic retinopathy (OIR).
Methods:
Twenty-two mice were exposed to 77% oxygen to induce OIR, while 23 age-matched control mice were raised in room air (RA). In vivo fluorescein angiography (FA), spectral-domain optical coherence tomography (SD-OCT), and focal electroretinography (fERG) were performed at P19, P24, P32, and P47, followed by histological assessments of retinal morphology, gliosis, microglia activation, and apoptosis.
Results:
FA in OIR mice showed capillary attrition despite peripheral revascularization. Inner retina thinning was detected with SD-OCT; outer and inner retinal dysfunction were demonstrated with fERG. Histology of the OIR mice exhibited a thin, disorganized structure. Immunohistochemistry showed increased gliosis, microglial activation, and apoptosis with increasing age from P19 to P47. The synapses between rod photoreceptor cells and rod bipolar cells were ectopically localized in the OIR mice.
Conclusions:
We demonstrated histological evidence of persistent ectopic synapses, prolonged cellular apoptosis, and gliosis in the OIR retina that corresponded with long-term in vivo evidence of capillary attrition, inner retinal thinning, and dysfunction despite full peripheral revascularization. Further studies on the mechanisms underlying these persistent phenotypes could enhance our understanding of ROP pathogenesis and lead to new therapeutic targets to preserve visual function in premature infants.
