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Updated: Aug 6, 2025
Monitoring Dynamic Growth of Retinal Vessels in Oxygen-Induced Retinopathy Mouse Model
Published on: April 2, 2021
FGF21 via mitochondrial lipid oxidation promotes physiological vascularization in a mouse model of Phase I ROP
Zhongjie Fu1, Pia Lundgren2, Aldina Pivodic2
1Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Insights
High blood sugar in premature infants increases the risk of retinopathy of prematurity (ROP). Fibroblast growth factor 21 (FGF21) may prevent this blinding condition by promoting healthy retinal vascular development.
Area of Science:
- Ophthalmology
- Neonatology
- Endocrinology
Background:
- Hyperglycemia in premature infants is linked to retinopathy of prematurity (ROP), a leading cause of blindness.
- Neovascular ROP (Phase II) is a pathological response to suppressed physiological retinal vascular development (Phase I).
Purpose of the Study:
- To investigate the role of fibroblast growth factor 21 (FGF21) in regulating physiological retinal vascular development.
- To explore potential therapeutic strategies for preventing neovascular ROP.
Main Methods:
- Studied the effects of hyperglycemia on retinal vascular growth in neonatal mice.
- Administered FGF21 and assessed its impact on retinal vascularization, adiponectin (APN) levels, and mitochondrial fatty acid oxidation.
- Analyzed clinical data on lipid intake in preterm infants with varying ROP severity.
Main Results:
- Hyperglycemia suppressed physiological retinal vascular growth and decreased FGF21 expression in mice.
- FGF21 administration promoted physiological retinal vascular growth, an effect dependent on APN and mitochondrial fatty acid oxidation.
- Preterm infants with severe neovascular ROP had lower enteral lipid intake compared to those with non-severe ROP.
Conclusions:
- FGF21 plays a crucial role in promoting physiological retinal vascular development.
- Adequate enteral lipid intake and potentially increased FGF21 levels may prevent Phase I retinopathy, thereby reducing the risk of neovascular ROP.
Abstract:
Hyperglycemia in early postnatal life of preterm infants with incompletely vascularized retinas is associated with increased risk of potentially blinding neovascular retinopathy of prematurity (ROP). Neovascular ROP (Phase II ROP) is a compensatory but ultimately pathological response to the suppression of physiological postnatal retinal vascular development (Phase I ROP). Hyperglycemia in neonatal mice which suppresses physiological retinal vascular growth is associated with decreased expression of systemic and retinal fibroblast growth factor 21 (FGF21). FGF21 administration promoted and FGF21 deficiency suppressed the physiological retinal vessel growth. FGF21 increased serum adiponectin (APN) levels and loss of APN abolished FGF21 promotion of physiological retinal vascular development. Blocking mitochondrial fatty acid oxidation also abolished FGF21 protection against delayed physiological retinal vessel growth. Clinically, preterm infants developing severe neovascular ROP (versus non-severe ROP) had a lower total lipid intake with more parenteral and less enteral during the first 4 weeks of life. Our data suggest that increasing FGF21 levels in the presence of adequate enteral lipids may help prevent Phase I retinopathy (and therefore prevent neovascular disease).
