AUTHOR=Li Zuohong , Chen Jianping , Lei Lei , Jiang Nan , Zhu Yanling , Jia Yu , Zhuo Yehong , Su Wenru 

TITLE=Laquinimod Inhibits Inflammation-Induced Angiogenesis in the Cornea

JOURNAL=Frontiers in Medicine

VOLUME=7

YEAR=2020

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.598056

DOI=10.3389/fmed.2020.598056

ISSN=2296-858X

ABSTRACT=<p><bold>Background:</bold> Inflammation-induced angiogenesis plays a critical role in many eye diseases, and abnormal angiogenesis inhibition is regarded as a therapeutic approach. Here, we examined the effects of laquinimod on inflammatory corneal angiogenesis.</p><p><bold>Methods:</bold> Mouse model of corneal neovascularization was induced by NaOH. Laquinimod or control vehicle were topically applied to alkali-treated eyes twice a day for 10 days. Corneal neovascularization, infiltrating inflammatory cells, and the levels of chemokines, pro-inflammatory cytokines were assessed. RAW cells and human umbilical vein endothelial cells were used <italic>in vitro</italic> to further explore the underlying mechanisms of the effects of laquinimod on inflammation-induced angiogenesis.</p><p><bold>Results:</bold> Topical administration of laquinimod to the injured corneas dramatically inhibited alkali-induced corneal neovascularization and decreased inflammatory cell (such as macrophage) infiltration in a corneal injury mouse model. Laquinimod significantly downregulated the expression of chemokines (monocyte chemotactic protein-1 and macrophage inflammatory protein-1), pro-inflammatory cytokines (interleukin-1β and tumor necrosis factor-alpha), vascular endothelial growth factor, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 and apoptosis-associated speck-like protein containing C-terminal caspase-recruitment domain adaptor protein in both injured corneas and RAW cells. <italic>In vitro</italic>, laquinimod also dramatically inhibited the proliferation, migration and tube formation of human umbilical vein endothelial cells.</p><p><bold>Conclusion:</bold> Laquinimod inhibits inflammation-induced angiogenesis in the cornea. These results suggest that laquinimod is a potential new therapeutic option for corneal neovascularization and other angiogenesis-associated diseases.</p>