Associations between VEGF isoforms and impending retinopathy of prematurity

Abstract

Background/Objective Vascular Endothelial Growth Factor (VEGF) is the main driver of angiogenesis during neurodevelopment (i.e., brain and retina). VEGF165 and VEGF121 are the two most prevalent human VEGF isoforms. Although retinopathy of prematurity (ROP), a neuroretinal disorder, is associated with VEGF dysregulation, little is known about the interaction of VEGF isoforms on neuroretinal angiogenesis. We hypothesized that: (a) A specific VEGF165/VEGF121 correlation, at a given time point, is associated with normal retinal development (no ROP) and (b) An altered correlation, of such, is associated with aberrant retinal development (ROP). Utilizing pre‐collected dried blood spots (DBS) from <1‐week‐old preterm infants, we aimed to determine whether correlations between VEGF165 and VEGF121 precede the diagnosis of early stage, non‐proliferative ROP (NP‐ROP). Methodology We conducted a case/control study, utilizing DBS from 65 preterm infants. We measured DBS levels of VEGF165 on the Mesoscale Discovery Platform and VEGF121 via Cloud Clone Elisa Assay. Results In infants with NP‐ROP, VEGF165 is significantly higher in males (than females). In infants without ROP, there is a significant correlation between VEGF165 and VEGF121 in females (but not males). In infants with NP‐ROP, the opposite is so; there is a significant correlation between VEGF165 and VEGF121 in males (but not females). Conclusions This pilot study, utilizing de‐identified data, suggests the potential importance of examining interactions between VEGF isoforms, at <1 week after birth, to better understand ROP development. Our study also suggests that retinal angiogenesis may not be a sex‐neutral process. A prospective study is needed to confirm our novel findings.

Genetic Polymorphisms of Vascular Endothelial Growth Factor in Neonatal Pathologies: A Systematic Search and Narrative Synthesis of the Literature

“…A case–control study of 65 preterm infants showed that VEGF165 and VEGF121, the two most prevalent human VEGF isoforms, are present in premature infants who did not develop retinopathy [ 101 ]. Kwinta et al, in a study on 181 Polish preterm newborns, showed that the carriage of polymorphic allele -460 T was significantly higher in ROP infants who needed treatment as compared to the no ROP infants [ 102 ].…”