Role of Periostin in Choroidal Fibrovascular Membrane Formation

Abstract

Purpose: The pathogenesis of choroidal fibrovascular membrane (FVM) formation remains unclear. Periostin is a matricellular protein involved in tissue and vascular remodeling. We previously reported the increased expression of periostin in FVMs obtained from patients with proliferative diabetic retinopathy (Yoshida et al IOVS 2011). The purpose of this study was to investigate the role of periostin in choroidal FVM formation.

Methods: We generated mouse laser-induced choroidal neovascularization model (CNV) using C57BL/6 wild type (WT) and periostin knock out (KO) mice. The concentration of periostin in retinal pigment epithelium (RPE)/choroid complex from WT CNV mice were measured by ELISA. Periostin localization in choroidal FVM obtained from CNV mice and from patients with age-related macular degeneration (AMD) was evaluated by immunohistochemical analysis. We also quantified the volume of CNV and the degree of fibrosis in FVM using choroidal flat mount of WT and periostin KO mice at 7 or 21 days after laser injury.

Results: ELISA showed that periostin concentrations in mouse CNV increased and reached a peak at 14 days after laser coagulation. Immunohistochemical analysis showed that periostin was expressed in RPE cells in choroidal FVM of both CNV mice and AMD patients. At 7 days after laser injury, the volume of CNV and the degree of fibrosis didn’t differ between WT and periostin KO mice. At 21 days after laser injury, the amount and density of collagen type 1 in FVM were significantly reduced in periostin KO mice compared to WT mice (p<0.01), while the volume of CNV was not significantly altered.

Conclusions: These results suggest that periostin plays a role in fibrosis of choroidal FVM formation.

Keywords: 453 choroid: neovascularization • 519 extracellular matrix • 654 proliferation