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Updated: Apr 20, 2026
Monitoring Dynamic Growth of Retinal Vessels in Oxygen-Induced Retinopathy Mouse Model
Published on: April 2, 2021
Pathophysiology and mechanisms of severe retinopathy of prematurity
1John A. Moran Eye Center, University of Utah, Salt Lake City, Utah.
Insights
Retinopathy of prematurity (ROP) is a leading cause of childhood blindness in premature infants. Understanding vascular endothelial growth factor (VEGF) signaling in animal models is key to developing targeted treatments for ROP.
Area of Science:
- Ophthalmology
- Developmental Biology
- Translational Science
Background:
- Retinopathy of prematurity (ROP) is a significant cause of childhood blindness, particularly with increasing premature births globally.
- Aberrant angiogenesis leading to fibrovascular retinal detachment underlies severe ROP, necessitating study of normal and pathologic developmental processes.
- Vascular Endothelial Growth Factor (VEGF) signaling plays a critical role in both normal and aberrant angiogenesis relevant to ROP.
Purpose of the Study:
- To review translational science findings from animal models of oxygen-induced retinopathy (OIR) that represent human ROP.
- To elucidate mechanisms of aberrant retinal angiogenesis in ROP, focusing on VEGF signaling pathways.
- To discuss potential therapeutic strategies targeting VEGF signaling for ROP treatment.
Main Methods:
- Review of studies using animal models of oxygen-induced retinopathy (OIR) that mimic human ROP.
- Analysis of signaling pathways involving hypoxia-inducible factors, VEGF, oxidative species, and neuroprotective factors.
- Examination of the role of VEGF receptor 2 signaling in aberrant vascular growth.
Main Results:
- Over-activation of VEGF receptor 2 signaling drives aberrant blood vessel growth into the vitreous, rather than the retina.
- Targeting specific retinal cells offers a strategy to inhibit aberrant angiogenesis and promote normal vascular development.
- Both broad and targeted inhibition of VEGF bioactivity can lead to toxicity, highlighting the need for nuanced approaches.
- VEGF plays a role in neuroprotection during retinal development.
Conclusions:
- Targeted inhibition of VEGF signaling, rather than broad anti-VEGF treatments, shows promise for future ROP therapies.
- Understanding the complex role of VEGF in retinal development and disease is crucial for effective treatment.
- Further research into cell-specific targeting and VEGF's neuroprotective functions is warranted for advancing ROP care.
Abstract:
Retinopathy of prematurity (ROP) affects only premature infants, but as premature births increase in many areas of the world, ROP has become a leading cause of childhood blindness. Blindness can occur from aberrant developmental angiogenesis that leads to fibrovascular retinal detachment. To treat severe ROP, it is important to study normal developmental angiogenesis and the stresses that activate pathologic signaling events and aberrant angiogenesis in ROP. Vascular endothelial growth factor (VEGF) signaling is important in both physiologic and pathologic developmental angiogenesis. Based on studies in animal models of oxygen-induced retinopathy (OIR), exogenous factors such as oxygen levels, oxidative stress, inflammation, and nutritional capacity have been linked to severe ROP through dysregulated signaling pathways involving hypoxia-inducible factors and angiogenic factors like VEGF, oxidative species, and neuroprotective growth factors to cause phases of ROP. This translational science review focuses on studies performed in animal models of OIR representative of human ROP and highlights several areas: mechanisms for aberrant growth of blood vessels into the vitreous rather than into the retina through over-activation of VEGF receptor 2 signaling, the importance of targeting different cells in the retina to inhibit aberrant angiogenesis and promote physiologic retinal vascular development, toxicity from broad and targeted inhibition of VEGF bioactivity, and the role of VEGF in neuroprotection in retinal development. Several future translational treatments are discussed, including considerations for targeted inhibition of VEGF signaling instead of broad intravitreal anti-VEGF treatment.
