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Topical Area: Maternal, Perinatal and Pediatric Nutrition

Maternal, Perinatal and Pediatric Nutrition (II) (Poster Session)

(P18-063-23) Folic Acid Supplementation Decreased Pathological Retinal Angiogenesis in Mice Modeling Retinopathy of Prematurity

Sunday, July 23, 2023
11:45 AM – 12:45 PM ET
Location: Poster Board 537

    Presenting Author(s)

  • HY

    Hitomi Yagi, MD

    Research fellow
    Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School
    Brookline, Massachusetts, United States

    • Co-Author(s)

  • Myriam Boeck, MD (she/her/hers)

    Research Fellow
    Boston Children's Hospital, Harvard Medical School
    Boston, Massachusetts, United States

  • MK

    Minji Ko

    Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School

  • JY

    Jay Yang

    Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School

  • KN

    Katherine Neilsen

    Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School

  • LS

    Lois Smith

    Boston Children's Hospital

  • ZF

    Zhongjie Fu

    Instructor
    Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School
    Boston, Massachusetts, United States

Disclosure(s):
Hitomi Yagi, MD: No relevant financial relationship(s) with ineligible companies to disclose.
Myriam Boeck, MD: No relevant financial relationship(s) with ineligible companies to disclose.


Objectives: Neovascular retinopathy of prematurity (ROP) can cause blindness in premature infants. Folate is critical for fetal development, and folate deficiency occurs in premature infants as the demands for growth may exceed the intake of folate. Premature infants with anemia respond well to folic acid therapy and premature infants who remain severely anemic are more likely to develops ROP than less anemic infants. However, the association between folic acid and ROP is still unknown.

Methods: Mouse oxygen-induced retinopathy (OIR) was used to model proliferative ROP. C57BL/6J mice pups and their nursing dam were exposed to 75% oxygen from postnatal day (P) 7 to P12 and returned to room air at P12 until P17. The pups were treated with either folic acid (0.5mg/kg) or vehicle intraperitoneally from P7 to P11. At P17, retinas were collected and vessels stained with isolectin. Alternatively, we exposed the nursing dam to folic acid deficient or control diet from P1 to P12 and examined the pup retinas at P17. The percentage of retinal neovascularization (NV) of the total retinal area was quantified using image J. Unpaired t-test, Welch’s test, or Mann-Whitney test was used to compare the groups. 

Results: In mouse OIR, early folic acid supplementation to pups significantly decreased retinal NV area, (particularly those pups with low body weight) (0.69±0.15% with folic acid vs. 1.00±0.28% without folic acid, p< 0.001). Deficiency of folic acid in maternal diet at the early stage significantly worsened retinal NV versus controls (1.33±0.34% vs. 1.00±0.30%, p< 0.01).

Conclusions: Our results suggest that early folic acid deficiency worsens, and early folic acid supplementation decrease retinal NV in OIR pups. Folic acid could be a potential target in helping to prevent ROP progression.

Funding Sources: The research was funded by NIH, Boston Children's Hospital (including OFD/BTREC/CTREC, Ophthalmology Foundation), Mass Lions Eye Foundation and Blind Children’s Center (ZF); NIH, Boston Children’s Hospital and Mass Lions Eye Foundation (LEHS).