PDGFRβ blockade inhibits choroidal neovascularization and fibrosis in a laser-induced CNV model in mice

Abstract

Purpose : Anti-vascular endothelial growth factor (VEGF) agents have revolutionized the treatment of wet age-related macular degeneration (AMD). However, it has been recently reported that subretinal fibrosis develops approximately in half of all anti-VEGF-treated cases within 2 years and is associated with poor visual prognosis. Therefore, it is necessary to develop a novel therapeutic approach to treat both choroidal neovascularization (CNV) and subretinal fibrosis. The purpose of this study is to investigate whether blockade for platelet-derived growth factor receptor β (PDGFRβ) inhibits the formation of CNV and fibrosis in a laser-induced CNV model in mice.

Methods : CNV was generated by laser photocoagulation (532nm, 180mW, 75μm) in male C57BL/6J mice aged 6-8 weeks. PDGFRβ neutralizing antibody or isotype-matched control antibody was injected into the vitreous cavity immediately after laser photocoagulation. Retinal pigment epithelium (RPE)-choroid flatmounts were harvested and stained with isolectin B4 and anti-mouse type I collagen antibody to measure the size of CNV and fibrosis, respectively, at days 7 and 21. RPE-choroid complex was also harvested 3 days after laser injury and the mRNA level of Acta2 (gene symbol for α-SMA) was analyzed by real-time qPCR.

Results : PDGFRβ blockade attenuated the size of CNV and fibrosis (CNV, 8332±2240.7µm²; fibrosis, 7154.2±1859.1µm²) compared to the control (CNV, 13033.7±3092.8µm²; fibrosis, 11078.1±3714.3µm², n=8, p<0.01) at 7 days after laser injury. At 21 days after laser photocoagulation, PDGFRβ blockade suppressed the size of fibrosis (5655±1471.7µm²), compared to the control (10717±3628.9µm², n=6, p<0.01). Real-time qPCR showed that PDGFRβ blockade inhibited the upregulation of Acta2 expression 3 days after laser injury by 37.5% (n=6, p<0.01).

Conclusions : The current data suggest that PDGFRβ is an attractive molecular target in the prevention of subretinal fibrosis in AMD.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.