主催: The Japanese Pharmacological Society, The Japanese Society of Clinical Pharmacology
会議名: WCP2018 (18th World Congress of Basic and Clinical Pharmacology)
開催地: Kyoto
開催日: 2018/07/01 - 2018/07/06
Background: Diabetic Retinopathy (DR) is one of the most common complications of diabetes and the main cause of vision impairment in the working-age population. Current treatments of DR include intraocular injection of anti-VEGF or steroids despite safety concerns. The aim of the present study was to explore the role of placental growth factor (PlGF) as new pharmacological target in DR.
Methods: Primary human retinal endothelial cells (HREC; Innoprot) were used in this study. We assessed TNF-α, VEGF and ERK in HREC exposed (48 h) with high glucose (40 mM) with or without anti-PlGF antibody treatment at different concentrations (from 1 to 50 μg/ml) by ELISA and Western blot. The effects of anti-PlGF antibody treatment were compared with aflibercept, a VEGF-trap, in order to discriminate the contribution of PlGF inhibition. The viability of HREC was determined using a colorimetric MTT assay. Cellular damage was also assessed by LDH release into the medium.
Results: Anti-PlGF protects HREC 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 (40 pg/ml) and the VEGF (80 pg/ml) levels that were significantly (p<0.01) attenuated, in a concentration-dependent manner, by anti-PlGF treatment. No significant effects were observed with aflibercept treatment, except for VEGF levels.
Conclusions: In conclusion, our data indicate that selective inhibition of PlGF protects HREC 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. Such a mechanism, partially distinct from VEGF blockade, if occurring in vivo may contribute to the potential therapeutic effect of anti-PlGF antibody in diabetic retinopathy.
