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Updated: Apr 17, 2026
In Vivo Multimodal Imaging and Analysis of Mouse Laser-Induced Choroidal Neovascularization Model
Published on: January 21, 2018
Nanoparticle-mediated expression of a Wnt pathway inhibitor ameliorates ocular neovascularization
Zhongxiao Wang1, Rui Cheng1, Kyungwon Lee1
1From the Department of Ophthalmology, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China (Z.W., X.X.); Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City (Z.W., R.C., K.L., L.D., J.-x.M.); Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora (P.T., U.B.K.); Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China (L.D.); and Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, MA (J.C.).
Objective:
The deficiency of very low-density lipoprotein receptor resulted in Wnt signaling activation and neovascularization in the retina. The present study sought to determine whether the very low-density lipoprotein receptor extracellular domain (VLN) is responsible for the inhibition of Wnt signaling in ocular tissues.
Approach And Results:
A plasmid expressing the soluble VLN was encapsulated with poly(lactide-co-glycolide acid) to form VLN nanoparticles (VLN-NP). Nanoparticles containing a plasmid expressing the low-density lipoprotein receptor extracellular domain nanoparticle were used as negative control. MTT, modified Boyden chamber, and Matrigel (™) assays were used to evaluate the inhibitory effect of VLN-NP on Wnt3a-stimulated endothelial cell proliferation, migration, and tube formation. Vldlr(-/-) mice, oxygen-induced retinopathy, and alkali burn-induced corneal neovascularization models were used to evaluate the effect of VLN-NP on ocular neovascularization. Wnt reporter mice (BAT-gal), Western blotting, and luciferase assay were used to evaluate Wnt pathway activity. Our results showed that VLN-NP specifically inhibited Wnt3a-induced endothelial cell proliferation, migration, and tube formation. Intravitreal injection of VLN-NP inhibited abnormal neovascularization in Vldlr(-/-), oxygen-induced retinopathy, and alkali burn-induced corneal neovascularization models, compared with low-density lipoprotein receptor extracellular domain nanoparticle. VLN-NP significantly inhibited the phosphorylation of low-density lipoprotein receptor-related protein 6, the accumulation of β-catenin, and the expression of vascular endothelial growth factor in vivo and in vitro.
Conclusions:
Taken together, these results suggest that the soluble VLN is a negative regulator of the Wnt pathway and has antiangiogenic activities. Nanoparticle-mediated expression of VLN may thus represent a novel therapeutic approach to treat pathological ocular angiogenesis and potentially other vascular diseases affected by Wnt signaling.
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