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=

Background: 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.

Methods: 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 in vitro to further explore the underlying mechanisms of the effects of laquinimod on inflammation-induced angiogenesis.

Results: 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. In vitro, laquinimod also dramatically inhibited the proliferation, migration and tube formation of human umbilical vein endothelial cells.

Conclusion: 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.