Protective effects of folic acid supplementation on retinal neovascularization in the mouse model of retinopathy of prematurity

Abstract

Purpose : Retinopathy of prematurity (ROP) is the major cause of blindness in children, affecting about 16,000 premature infants per year in the US. Folate is an essential nutrient for fetal development and growth, and shortage of maternal folic acid intake causes embryonic eye defects during gestation. Premature infants have high risk for folate deficiency as the demands for growth exceed the intake of folate. However, the contribution of folate to ROP risk remains unknown.

Methods : The mouse model of oxygen-induced retinopathy (OIR) was used to mimic ROP. Neonatal mice and their nursing dams were exposed to 75% oxygen between postnatal day 7 (P7) and P12 and then returned to room air on P12. Pups received intraperitoneal injection of either folic acid (o.5mg/kg) or vehicle from P7 to P11, or P12 to P16. Alternatively, nursing dams were fed with folic acid deficient or control diet from P1 to P11 in OIR model. At P17, retinal neovascularization (NV) was evaluated by isolectin staining. The percentage of retinal NV of the total retinal area was quantified using image J. Unpaired t-test, Welch’s test, or Mann-Whitney test was used for comparison of results.

Results : For the early direct supplementation of folic acid to pups, retinal NV was decreased versus control group (0.69±0.15% with folic acid vs. 1.00±0.28% with vehicle control, p<0.001). Deficiency of folic acid in maternal diet versus control diet at the early stage also increased retinal NV (1.33±0.34% vs. 1.00±0.30%, p<0.01).

Conclusions : Early folic acid deficiency worsens while early folic acid supplementation protects against retinal NV in OIR. Folic acid might be a new, safe treatment for ROP at an early stage.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.