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Updated: May 25, 2025
Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
Folic Acid Supplementation Inhibits Proliferative Retinopathy of Prematurity
Shen Nian1,2, Yan Zeng1, Katarina E Heyden3
1Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Insights
Folic acid deficiency worsens retinopathy of prematurity (ROP) in mice. Supplementation with folic acid may offer a safe, early-stage treatment for ROP, a leading cause of childhood blindness.
Area of Science:
- Ophthalmology
- Neonatology
- Nutritional Science
Background:
- Retinopathy of prematurity (ROP) is a leading cause of childhood blindness.
- ROP is a biphasic disease involving abnormal retinal vessel growth.
- Premature infants are at high risk for folate deficiency, but its role in ROP is unclear.
Purpose of the Study:
- To investigate the role of folic acid in retinopathy of prematurity (ROP).
- To determine if folic acid supplementation can prevent or treat ROP.
Main Methods:
- Mouse oxygen-induced retinopathy (OIR) model was used.
- Maternal diet or pup injections manipulated folic acid levels.
- Gene expression and retinal folate levels were analyzed.
Main Results:
- Folic acid deficiency exacerbated OIR, while supplementation suppressed it.
- Folate cycle genes were downregulated in OIR retinas and expressed in Müller glia.
- Folic acid reduced pro-angiogenic signaling in retinal Müller glia.
Conclusions:
- Folic acid plays a critical role in regulating retinal angiogenesis.
- Folic acid supplementation may be a safe and effective early treatment for ROP.
Background:
Retinopathy of prematurity (ROP) is the major cause of blindness in children. It is a biphasic disease with retinal vessel growth cessation and loss (Phase I) followed by uncontrolled retinal vessel growth (Phase II). Folate is an essential nutrient for fetal development and growth. Premature infants have a high risk for folate deficiency. However, the contribution of folate to ROP risk remains unknown.
Methods:
In mouse oxygen-induced retinopathy (OIR), the nursing dams were fed with a folic acid-deficient or control diet after delivery until the end of hyperoxia. Alternatively, pups received direct injection of either folic acid or vehicle during Phase I hyperoxia. Genes involved in the folate cycle and angiogenic responses were examined using real-time PCR. Total retinal folate levels were measured with the Lactobacillus casei assay.
Results:
Maternal folic acid deficiency in early life exacerbated pathological retinal vessel growth, while supplementation with folic acid suppressed it. Genes involved in the folate cycle were downregulated in Phase I OIR retinas and were highly expressed in Müller glia. Folic acid reduced pro-angiogenic signaling in cultured rat retinal Müller glia in vitro.
Conclusions:
Appropriate supplementation of folic acid might be a new and safe treatment for ROP at an early stage.
