GLI3 is differentially expressed in the placenta and systemic circulation relative to ROP development

Abstract

Purpose : Retinopathy of prematurity (ROP) disrupts postnatal retinal vascular development within the incompletely vascularized retina of preterm infants; resultant visual impairment accounts for up to 40% of all childhood blindness worldwide. ROP cannot be cured or prevented. Our group has identified a novel variant in the intron of the sonic hedge-hog pathway gene, GLI3, which reaches genome-wide significance in a multiethnic cohort. GLI3 has not been studied within the context of ROP; the goal of this work is to determine the placental and peripheral expression of GLI3 within preterm infants with risk for ROP.

Methods : We utilized our existing Maternal-Infant Biorepository (MIP) to analyze GLI3 expression within placental tissue and peripheral blood from preterm infants with (n=14) or without (n=16) ROP. Whole transcriptome analysis was performed on fetal surface placental tissue and differentially expressed genes identified relative to ROP clinical outcomes as previously published by our group with confirmatory RT-PCR analysis. Systemic expression of GLI3 was assessed using ELISA analysis of infant plasma samples at two timepoints, 30-33 and 34-36 weeks post-gestational age (GA). Statistical associations were assessed using a paired t-test.

Results : We found that GLI3 was expressed within the placenta and peripheral circulation for infants born preterm with ROP risk. Placental GLI3 mRNA expression was reduced for infants with subsequent ROP development (-2.117; adjp 0.014) which was confirmed using RT-PCR. At 30-33 weeks post-gestational age, GLI3 plasma protein expression was increased for infants with subsequent ROP development compared to those without (p≤0.05). However, during the average age range for ROP development, 34-36 weeks GA, we found a statistically significant decrease in GLI3 expression for infants with ROP disease (p<0.01) which was most significant for infants with severe disease (≥stage 3).

Conclusions : Our group previously identified a novel variant within GLI3 correlating with ROP severity. We now show that GLI3 expression within the placenta and infant systemic circulation statistically correlates with ROP development and severity. Future work will examine the potential functional implications for this correlation and for the described variant to GLI3 expression.

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