Abstract
Purpose :
Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family. PlGF exerts its role through activation of VEGF Receptor 1 (Flt-1). Normal physiologic function and maintenance of tissue integrity require low levels of systemic VEGF activity. Suppression of this baseline activity by anti-VEGF could cause ADRs. The aim of the present study was to investigate the effects of selective anti-PlGF on retinal endothelial cells exposed to high glucose.
Methods :
Human retinal endothelial cells (HRECs) were exposed (48 h) to high glucose levels (40 mM) with or without anti-PlGF antibody at different concentrations (from 1 to 50 µg/ml). TNF-α, VEGF and ERK were assessed by ELISA or Western blot analysis. Cellular damage was also assessed by LDH release measurement.
Results :
Anti-PlGF protects HRECs against the damage elicited by high glucose. High glucose significantly (p<0.01) increased the levels of activated/phosphorylated ERK, while anti-PlGF treatment significantly (p<0.01) counteracted ERK phosphorylation, induced by high glucose, in a concentration-dependent manner. HREC exposed to high glucose increased the TNF-α and the VEGF levels that were significantly (p<0.01) attenuated, in a concentration-dependent manner, by anti-PlGF treatment.
Conclusions :
The present findings indicate that selective inhibition of PlGF protects HRECs against high glucose-induced damage through the inhibition of ERK pathway. Moreover the expression of cytokines such as TNF-α and VEGF were also decreased by anti-PlGF treatment. This mechanism, partially distinct from VEGF blockade, if occurring in vivo may contribute to the potential therapeutic effect of anti-PlGF antibody in diabetic retinopathy.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.