Preeclampsia-mediated ROP Protection is Associated with Differential Placental Proteome Expression

Abstract

Purpose : Retinopathy of prematurity (ROP) accounts for up to 40% of all childhood blindness worldwide though cannot be cured or prevented. Maternal preeclampsia correlates with reduced risk for ROP development in preterm infants. Preeclampsia is a condition of placental insufficiency; our group has identified differential placental RNA expression which correlates with ROP and preeclamptic clinical outcomes. We sought to validate this finding at the protein level within fetal placental tissue, with greatest relevance to postnatal infant circulation and clinical outcomes.

Methods : We utilized our existing Maternal-Infant Biorepository (MIP) to analyze the placental proteome for preterm infants with (n=14) or without (n=15) ROP development representing 14 infants born with gestational exposure to preeclampsia and 15 control infants. Trophoblast regions of fetal placenta were identified, harvested, and analyzed by high resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS). To determine the significance of protein abundance changes between the different groups, protein abundance measures were log2-transformed and statistical significance calculated using standard parametric tests and Bonferroni correction to control for multiple testing.

Results : Among the >7000 proteins quantified, 462 proteins were significantly altered (298 downregulated; 164 upregulated) relative to ROP development (p≤0.05). Similarly, we found 542 proteins altered (278 downregulated; 264 upregulated) relative to preeclampsia (p≤0.01). Principle component analysis demonstrated segregation of proteome expression for infants born with gestational exposure to preeclampsia without ROP development (n= 8; 185 proteins significantly elevated [p≤0.01]) compared to those without exposure to gestational preeclampsia who developed ROP (n=8; 219 proteins significantly elevated [p≤0.01]) with 60.9% variance explained.

Conclusions : Herein, we utilize deep MS-based placental tissue analysis to demonstrate significant proteome alterations correlating with gestational exposure to preeclampsia and ROP avoidance in at-risk preterm infants. Together with our prior work, we demonstrate that both RNA and protein level differential expression correlate with preeclampsia-mediated ROP protection, which may allow for greater insight into the molecular basis for ROP risk going forward.

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