Periostin promotes inflammation and neovascularization in atopic keratoconjunctivitis.

Abstract

Atopic keratoconjunctivitis (AKC) is a chronic allergic conjunctival disease accompanied by corneal lesions, including epithelial damage, and neovascularization. Periostin, a downstream molecule of type 2 inflammation, is highly expressed in tears and conjunctiva of AKC patients and correlated with disease severity, but its involvement in the pathogenesis of AKC remains unclear. We have established facial atopic dermatitis with scratching (FADS) mice that spontaneously develop AKC-like ocular lesions with increased periostin expression and corneal neovascularization. Using FADS mice, we sought to clarify the functional role of periostin in the pathogenesis of AKC with the eventual goal of developing novel therapeutic strategies targeting the periostin/integrin α_Vβ₃ pathway. We generated periostin-deficient FADS mice and analyzed AKC-like ocular lesions, including corneal neovascularization. Moreover, we examined the effects of CP4715, an α_Vβ₃ integrin inhibitor, on the AKC-like ocular lesions in FADS mice. Genetic disruption and pharmacologic inhibition of the periostin/α_Vβ₃ integrin pathway ameliorated corneal epithelium hyperplasia with NF-κB activation, infiltration of mast cells, T_H2 cells, or neutrophils associated with type 2 or non-type 2 inflammation in the corneal stroma and conjunctiva in FADS mice. Moreover, we found that inhibiting the periostin/α_Vβ₃ integrin pathway decreased corneal neovascularization by reducing expression of VEGF-A/VEGF-R2 in corneal epithelium, stroma, and vascular endothelial cells. Periostin plays an important role in corneal neovascularization and in type 2 and non-type 2 inflammation in AKC-like ocular lesions of FADS mice. Targeting the periostin/α_Vβ₃ integrin pathway is a promising therapeutic strategy for treating AKC patients.