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Folic Acid Supplementation Inhibits Proliferative Retinopathy of Prematurity

ORCID
0000-0002-9684-0340
Affiliation
Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA;(S.N.);(Y.Z.);(H.Y.);(D.L.);(V.H.);(Z.H.);(C.W.);(K.N.)
Nian, Shen;
ORCID
0009-0004-3626-6801
Affiliation
Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA;(S.N.);(Y.Z.);(H.Y.);(D.L.);(V.H.);(Z.H.);(C.W.);(K.N.)
Zeng, Yan;
Affiliation
Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA;(K.E.H.);(M.S.F.)
Heyden, Katarina E.;
ORCID
0000-0001-9664-3518
Affiliation
Centre Hospitalier Universitaire Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada(J.-S.J.)
Cagnone, Gaël;
Affiliation
Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA;(S.N.);(Y.Z.);(H.Y.);(D.L.);(V.H.);(Z.H.);(C.W.);(K.N.)
Yagi, Hitomi;
ORCID
0000-0001-8343-4426
Affiliation
Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA;(S.N.);(Y.Z.);(H.Y.);(D.L.);(V.H.);(Z.H.);(C.W.);(K.N.)
Boeck, Myriam;
ORCID
0000-0002-5992-9039
Affiliation
Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA;(S.N.);(Y.Z.);(H.Y.);(D.L.);(V.H.);(Z.H.);(C.W.);(K.N.)
Lee, Deokho;
ORCID
0009-0003-5821-5477
Affiliation
Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA;(S.N.);(Y.Z.);(H.Y.);(D.L.);(V.H.);(Z.H.);(C.W.);(K.N.)
Hirst, Victoria;
Affiliation
Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA;(S.N.);(Y.Z.);(H.Y.);(D.L.);(V.H.);(Z.H.);(C.W.);(K.N.)
Hua, Zhanqing;
Affiliation
Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA;(S.N.);(Y.Z.);(H.Y.);(D.L.);(V.H.);(Z.H.);(C.W.);(K.N.)
Lee, Jeff;
ORCID
0009-0001-1471-5360
Affiliation
Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA;(S.N.);(Y.Z.);(H.Y.);(D.L.);(V.H.);(Z.H.);(C.W.);(K.N.)
Wang, Chaomei;
ORCID
0009-0007-4996-9380
Affiliation
Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA;(S.N.);(Y.Z.);(H.Y.);(D.L.);(V.H.);(Z.H.);(C.W.);(K.N.)
Neilsen, Katherine;
Affiliation
Centre Hospitalier Universitaire Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada(J.-S.J.)
Joyal, Jean-Sébastien;
Affiliation
Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA;(K.E.H.);(M.S.F.)
Field, Martha S.;
ORCID
0000-0002-8182-2983
Affiliation
Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA;(S.N.);(Y.Z.);(H.Y.);(D.L.);(V.H.);(Z.H.);(C.W.);(K.N.)
Fu, Zhongjie

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.

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Editor:
Germain, Pierre
Published in:
Biomolecules  
Vol. 15, No. 2 (19.02.2025)
Volume:
15
No.:
2
Date Issued:
19.02.2025
DOI:
10.3390/biom15020309
Language:
English
Type of Resource:
Text
Keywords:
retinopathy of prematurity; folate; neovascularization; angiogenesis; oxygen-induced retinopathy; retina
DDC:
610 Medizin und Gesundheit

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