Anti-apoptotic and anti-inflammatory effect of PD-L1 in Dry Eye Mouse Model

Abstract

Purpose : To examine the effects of programmed death-ligand1 (PD-L1) on apoptosis and inflammation through T-cell suppression in scopolamine- induced dry eye model.

Methods : We induced desiccation stress in female C57BL/6 mouse using scopolamine. The C57BL/6 mouse was divided into 3 groups: “Control”, “Desiccation”, and “Desiccation + PD-L1”; topical recombinant mouse PD-L1 was applied three times daily for 5 days. To investigate the effects of PD-L1 on T-cell in desiccation stress induced dry eye model, we used immunohistochemical analysis for CD3e and PD-L1, immunofluorescent staining for CD4 andIL-17 with 3 groups of mouse cornea. To evaluate the effect of PD-L1 on desiccation stress induced apoptosis, we performed Tunnel assay and measured expression of Bax by western blot usingprotein extracts of mouse cornea. Moreover, to determine the effects of PD-L1 on inflammation, we quantified the expression of nuclear factor-κB (NF-κB) activation and phosphorylated NF-κB inhibitor α (IκB-α) using western blot analysis with protein extracts of mouse cornea.

Results : CD3e, CD4, and IL-17 levels further increased by scopolamine induced desiccation stress, and induction of the T-cell markers was significantly decreased by PD-L1. In the desiccation stress induced mouse cornea, apoptotic and inflammatory proteins, Bax, phosphorylated NF-κB and phosphorylated IκB-α were also enhanced.. while these expreesion levels were markedly reduced by PD-L1.

Conclusions : PD-L1 had potent anti-inflammatory and anti-apoptotic effects in desiccation stress through T-cell suppression. Therefore, PD-L1 may represent a novel therapeutic approach to managing dry eye disease.

This is a 2020 ARVO Annual Meeting abstract.