Abstract
SARI (Suppressor of AP‐1, regulated by IFN‐β) is known to play an important role in some systemic disease processes such an inflammatory conditions and cancer. We hypothesize that SARI may also play a role in ocular diseases involving inflammation and neovascularization. To explore our hypothesis, further, we investigated an endotoxin‐induced uveitis (EIU) and experimental argon laser‐induced choroidal neovascularization (CNV) model in SARI wild‐type (SARIWT) and SARI‐deficient (SARI−/−) mice. Through imaging, morphological and immunohistochemical (IHC) studies, we found that SARI deficiency exacerbated the growth of CNV. More VEGF‐positive cells were presented in the retina of SARI−/− mice with CNV. Compared to SARIWT mice, more inflammatory cells infiltrated the ocular anterior segment and posterior segments in SARI−/− mice with EIU. Collectively, the results point to a potential dual functional role of SARI in inflammatory ocular diseases, suggesting that SARI could be a potential therapy target for ocular inflammation and neovascularization.
Highlights
Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among elderly people.[1]
Our results suggested that SARI deficiency promoted the expression of CCL 2 in endotoxin-induced uveitis (EIU) model (Figure 5E & F), which indicated that more CCL 2-positive cells infiltrated the extravascular uveal tissue
SARI inhibited the spread of Choroidal neovascularization (CNV), as shown by our high-resolution angiography study
Summary
Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among elderly people.[1]. SARI (Suppressor of AP-1, regulated by INF-β), called as BATF2, is a member of BATF (Basic leucine zipper (bZIP) transcription factor, ATF-like) family, which contains BATF (otherwise known as SFA2), BATF2 and BATF3 (otherwise known as JDP1 and p21SNFT).[10] Various studies have demonstrated the anti-tumour role of SARI in multiple cancers, including lung cancer,[11] prostate cancer,[12,13] B lymphoma[14] and colon cancer.[15,16] Previous studies by us indicated that SARI was down-regulated in colon cancer[15,17] and inhibits colon cancer growth through inhibiting the translational activity of HIF-1α/VEGF and tumour angiogenesis.[15] SARI is involved in innate immunity and infection immunity.[18,19] SARI protects mice from Mycobacterium tuberculosis and Listeria monocytogenes mediated Type 1 and Type 2 diseases.[18] During T cruzi infection, SARI functions as a negative regulator of IL-23a in innate immune cells.[19] We and a previous study by Kayama demonstrated the protective role of SARI in colitis through regulating macrophage infiltration.[20] Against this background, we speculated that SARI may have a role to play in preventing angiogenesis and inflammation responses in certain ocular diseases. The present study expands the understanding of SARI function and provides a novel therapy target for certain ocular diseases
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