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Updated: Mar 11, 2026
Oxygen-Induced Retinopathy Model for Ischemic Retinal Diseases in Rodents
Published on: September 16, 2020
Hyperoxia-Induced Proliferative Retinopathy: Early Interruption of Retinal Vascular Development with Severe and
Michelle Lajko1, Herminio J Cardona2, Joann M Taylor2
1Department of Ophthalmology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois, United States.
Insights
Bronchopulmonary dysplasia (BPD) in premature infants can cause retinopathy of prematurity. This study models BPD using hyperoxia, revealing severe retinal vascular disruption and inflammation in mice.
Area of Science:
- Ophthalmology
- Neonatology
- Developmental Biology
Background:
- Bronchopulmonary dysplasia (BPD) is a significant cause of illness in premature infants, linked to impaired lung development and postnatal complications.
- Infants with BPD receiving supplemental oxygen face an increased risk of retinopathy of prematurity.
Purpose of the Study:
- To investigate the impact of hyperoxia on retinal vasculature in a mouse model of BPD.
- To characterize the phenotype of hyperoxia-induced proliferative retinopathy (HIPR).
Main Methods:
- Neonatal mice were exposed to 75% oxygen from postnatal day 0 to 14 to model BPD.
- Retinal tissues were analyzed at P15, P21, and P28 for vascular integrity, thickness, protein levels (HIF-1α, NOX2, VEGF), and inflammatory markers (F4/80, CD45R).
Main Results:
- The hyperoxia-induced proliferative retinopathy (HIPR) model exhibited severe disruption of normal retinal vascular development.
- HIPR mice showed disorganized intra-retinal angiogenesis, persistent hyaloidal vasculature, thinner central retinas, and inflammation.
- Increased HIF-1α and VEGF levels, along with fibrinogen deposition and immune cell infiltration, were observed.
Conclusions:
- The developed mouse model effectively replicates severe retinal vascular abnormalities seen in BPD-related retinopathy.
- HIPR is characterized by disrupted vascular development, angiogenesis, inflammation, and retinal detachment, providing a valuable tool for further research.
Abstract:
Bronchopulmonary dysplasia (BPD) is a major cause of neonatal morbidity in premature infants, occurring as a result of arrested lung development combined with multiple postnatal insults. Infants with BPD exposed to supplemental oxygen are at risk of retinopathy of prematurity as well. Thus, we studied the effects of hyperoxia on the retinal vasculature in a murine model of BPD. The retinal phenotype of this model, which we termed hyperoxia-induced proliferative retinopathy (HIPR), shows severe disruption of retinal vasculature and loss of vascular patterning, disorganized intra-retinal angiogenesis, inflammation and retinal detachment. Neonatal mice were subjected to 75% oxygen exposure from postnatal day (P)0 to P14 to model BPD, then allowed to recover in room air for 1 (P15), 7 (P21), or 14 days (P28). We quantified retinal thickness, protein levels of HIF-1α, NOX2, and VEGF, and examined the cellular locations of these proteins by immunohistochemistry. We examined the retinal blood vessel integrity and inflammatory markers, including macrophages (F4/80) and lymphocytes (CD45R). Compared to controls, normal retinal vascular development was severely disrupted and replaced by a disorganized sheet of intra-retinal angiogenesis in the HIPR mice. At all time-points, HIPR showed persistent hyaloidal vasculature and a significantly thinner central retina compared to controls. HIF-1α protein levels were increased at P15, while VEGF levels continued to increase until P21. Intra-retinal fibrinogen was observed at P21 followed by sub-retinal deposition in at P28. Inflammatory lymphocytes and macrophages were observed at P21 and P28, respectively. This model presents a severe phenotype of disrupted retinal vascular development, intra-retinal angiogenesis inflammation and retinal detachment.
