The role of a novel regulator of Wnt signalling in ocular angiogenesis

Abstract

Purpose : Abnormal blood vessel formation is a hallmark of many blinding eye diseases, including proliferative diabetic retinopathy (PDR) and age-related macular degeneration (AMD). Our previous study showed a reduced expression level of a secreted frizzled related protein (SFRP) in vitreous of PDR patients as compared to that in control patients. The purpose of this study is to investigate the role of this SFRP in retinal vascular cell function and angiogenesis.

Methods : Recombinant human SFRP Fc chimera protein was generated and purified before being tested for its impact on human retinal endothelial cell (HREC) proliferation, ability to form tube like structure, and monocyte recruitment. Ex vivo assays including Choroid sprouting assay, aortic ring assay and metatarsal assay were used to study the impact of SFRP-Fc as well as N-terminal domain (SFRP-N-Fc) and C-terminal domain (SFRP-C-Fc) on angiogenesis. SFRP-Fc and SFRP-C-Fc were further evaluated in a mouse model of laser-induced choroidal neovascularization (CNV) and a rabbit model of persistent retinal neovascularization (PRNV).

Results : Our study demonstrated a strong inhibitory effect of SFRP on HREC proliferation, tube formation and monocyte adhesion. We further showed that the C-terminal domain of HREC is responsible for its anti-angiogenic function. Both SFRP-Fc and SFRP-C-Fc are able to inhibits vessel outgrowth as demonstrated in multiple ex vivo assays. Finally, our study revealed a potent anti-angiogenic effect of SFRP-Fc and SFRP-C-Fc in mouse model of laser-induced CNV and in rabbit model of PRNV.

Conclusions : This study revealed SFRP as a potent anti-angiogenic factor and its functional domain is located at the C-terminal region domain of the SFRP protein.

This is a 2020 ARVO Annual Meeting abstract.