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.
Highlights
Angiogenesis is vital for normal physiological processes and tissue repair, including growth, reproduction and wound healing [1, 2]
Laquinimod significantly downregulated the expression of chemokines, pro-inflammatory cytokines, 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
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
Summary
Angiogenesis is vital for normal physiological processes and tissue repair, including growth, reproduction and wound healing [1, 2]. Angiogenesis and the accompanying inflammatory responses induce disorganization of collagen fibrils and corneal neovascularization (CNV) and impair corneal clarity and vision [4]. The development of new strategies that inhibit inflammation-induced angiogenesis has become the primary goal for treating many corneal diseases. Macrophages and other inflammatory cell types secrete various proangiogenic and pro-inflammatory factors and markedly promote the inflammatory response by interacting with vascular tip cells, endothelial cells, progenitor cells and epithelial cells [5,6,7,8]. Some studies have suggested that macrophages play a pivotal role in the process of inflammatory CNV by providing proangiogenic and pro-inflammatory cytokines [9, 10]. Inflammation-induced angiogenesis plays a critical role in many eye diseases, and abnormal angiogenesis inhibition is regarded as a therapeutic approach. We examined the effects of laquinimod on inflammatory corneal angiogenesis
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