Suppression of Inflammatory Corneal Lymphangiogenesis by Application of Topical Corticosteroids

Abstract

Objectives:To analyze whether topical application of corticosteroids inhibits inflammatory corneal lymphangiogenesis and to study the potential underlying antilymphangiogenic mechanisms.Methods: Inflammatory corneal neovascularization was induced by suture placement, and the corneas were then treated with topical fluorometholone, prednisolone acetate, or dexamethasone sodium phosphate. After 1 week, the corneas were stained with lymphatic vessel endothelial hyaluronan receptor 1 for detection of pathological corneal lymphangiogenesis. The effect of these corticosteroids on macrophage recruitment was assessed via fluorescence-activated cell sorting analysis. The effect of these corticosteroids on proinflammatory cytokine expression by peritoneal exudate cells was tested via real-time polymerase chain reaction. Furthermore, the effect of steroid treatment on the proliferation of lymphatic endothelial cells was assessed via enzyme-linked immunosorbent assay.Results: Treatment with corticosteroids resulted in a significant reduction of inflammatory corneal lymphangiogenesis. The antilymphangiogenic effect of fluorometholone was significantly weaker than that of prednisolone and dexamethasone. Corneal macrophage recruitment was also significantly inhibited by the application of topical steroids. Treatment of peritoneal exudate cells with corticosteroids led to a significant downregulation of the RNA expression levels of tumor necrosis factor and interleukin 1␤. Additionally, proliferation of lymphatic endothelial cells was also inhibited.

Early effects of dexamethasone and anti-VEGF therapy in an inflammatory corneal neovascularization model

“…Generally, the penetration of topically instilled dexamethasone into the cornea is known from clinical experience and earlier experimental studies (Bessonova et al, 2011;Hoffart et al, 2010;Hos et al, 2011). Topical anti-VEGF antibodies have similarly shown good penetration into the cornea, particularly after local disruption of the epithelial barrier and induction of inflammation and angiogenesis (Rocher et al, 2011;Stevenson et al, 2012;Yoeruek et al, 2008).…”

In vivo imaging of lymphatic vessels in development, wound healing, inflammation, and tumor metastasis

“…Corticosteroids have been shown to block lymphangiogenesis induced by VEGF-C in the cornea (39) and by tumor cells (40). To investigate the effect of corticosteroids on lymphangiogenesis during skin wound healing, a set of Vegfr3 EGFPLuc females was treated with dexamethasone (Dex), a synthetic glucocorticoid with a potent anti-inflammatory activity, shown to prevent angiogenesis and lymphangiogenesis associated to chronic inflammation (41) and to block lymphatic vessel regeneration (42).…”

UV light crosslinking regresses mature corneal blood and lymphatic vessels and promotes subsequent high-risk corneal transplant survival

“…Although there are several possibilities to suppress actively outgrowing corneal BVs and LVs, such as the topical application of vascular endothelial growth factor (VEGF) inhibitors6, 7, 8, 9 and corticosteroids,10 as well as antisense oligonucleotide eye drops against insulin receptor substrate‐1,11 these methods cannot regress mature corneal vessels. For preexisting corneal BVs, only preclinical approaches like anti–VEGF‐B antibody fragment have been used,12 and fine needle diathermy united with anti‐VEGFs has been shown to regress mature BVs, while its effect on LVs is still unclear 13, 14, 15.…”