SOCS3 deletion in myeloid cells worsens retinal inflammation and increases angiogenesis in experimental autoimmune uveoretinitis

Abstract

Purpose: Myeloid-derived cells, including neutrophils and macrophages, are critically involved in retinal damage and angiogenesis in experimental autoimmune uveoretinitis (EAU). Suppressors of cytokine signalling (SOCS) proteins are negative-feedback regulators of the JAK/STAT pathway. The aim of this study is to investigate the effect of SOCS3 deletion in myeloid cells to EAU development and its associated angiogenesis.

Methods: EAU was induced in C57BL/6 (WT) and LysM-Cre-SOCS3^fl/fl mice. Retinal inflammation was evaluated clinically using the topical endoscopic fundus imaging (TEFI) system and optical coherence tomography (OCT), and pathologically by light microscopy. Retinal vascular leakage was examined by fluorescein fundus angiography (FFA) and angiogenesis was studied by confocal microscopy of retinal flatmounts. Real-time RT-PCR and Western blot were used to explore factors that were critically involved in inflammatory and angiogenic processes.

Results: TEFI and OCT investigations revealed more severe inflammation and tissue damage in LysM-Cre-SOCS3^fl/fl EAU mice compared to WT EAU mice. FFA and flatmount staining showed more angiogenic membrane in LysM-Cre-SOCS3^fl/fl EAU mice. In addition, the expression of IL-1β, CCL2 and VEGF-A in the retina was increased in LysM-Cre-SOCS3^fl/fl EAU mice, which was accompanied by enhanced pSTAT3 and pErk1/2 expression.

Conclusions: The deletion of SOCS3 in myeloid cells worsens retinal inflammation and increases retinal angiogenesis in EAU. SOCS3 may be a potential therapeutic target in autoimmune retinal inflammation and inflammation-induced angiogenesis.