Abstract
Purpose :
Increased serum levels of soluble E-selectin (sE-selectin) have been associated with treatment warranted retinopathy of prematurity (ROP) in preterm infants, suggesting sE-selectin as a potential serum marker to identify preterm infants at risk of developing ROP. However, few studies have investigated the mechanistic role of E-selectin in the pathologic features found in ROP. Here we tested the hypothesis that serum levels of sE-selectin would associate with retinal E-selectin expression during the development of intravitreal neovascularization in ROP. We used an experimental model of oxygen-induced retinopathy (OIR) in the rat to test the hypothesis.
Methods :
Litters of newborn rat pups were placed into an oxycycler and exposed to alternating 24hr periods of 50% and 10% oxygen for 14 days. At postnatal day (p)14, the litters were moved to room air (RA, 21% oxygen). Pups were sacrificed at p14 and p20, and serum and retinas were harvested to evaluate E-selectin expression. Serum levels of sE-selectin were measured using an ELISA assay, and retinal expression of the E-selectin gene, Sele, as well as Adam8 and Vegf, were measured using qRT-PCR. Samples from OIR treated pups were compared to those from age-matched RA-controls and analyzed using a one-way Anova.
Results :
Following OIR treatment, sE-selectin was upregulated in the serum of pups at p14 (p=0.038) and p20 (p=0.028) compared to RA-controls. Retinal Sele expression, increased over time in the retinas of OIR pups and was significantly increased at p20 compared to RA-controls (p=0.031). Expression of Vegf and the metalloprotease that cleaves cell bound E-selectin, Adam8, were significantly increased in OIR pups at p14 (p=0.029 and p=0.022) and p20 (p<0.001 and p=0.032) compared to RA-controls.
Conclusions :
Increased serum sE-selectin preceded the formation of intravitreal neovascularization, and both sE-selectin and retinal Sele expression were increased in association with the development of intravitreal neovascularization in the rat OIR model. sE-selectin levels were also increased in association with increased retinal Vegf and Adam8, suggesting a potential mechanism by which sE-selectin levels are increased by upregulated retinal E-selectin during the development of ROP.
This is a 2020 ARVO Annual Meeting abstract.