Protective Effects of Fucoidan on Epithelial-Mesenchymal Transition of Retinal Pigment Epithelial Cells and Progression of Proliferative Vitreoretinopathy

Cell Physiol Biochem. 2018;46(4):1704-1715. doi: 10.1159/000489246. Epub 2018 Apr 23.

Abstract

Background/aims: Proliferative vitreoretinopathy (PVR) is a severe blinding complication of rhegmatogenous retinal detachment. Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is thought to play a pivotal role in the pathogenesis of PVR. Fucoidan, a marine extract, reportedly has many benefits effects in a variety of tissues and organs such as anti-inflammation, anti-oxidative stress, and anti-carcinogenesis. In this study, we investigated the potential role of fucoidan on EMT in RPE cells and its effect on the development of PVR.

Methods: MTS, Transwell, and collagen gel contraction assays were employed to measure the viability, migration, and contraction of RPE cells, respectively. mRNA and protein expression were evaluated via real-time quantitative PCR and western blot analysis, respectively. In vivo, a pigmented rabbit model of PVR was established to examine the anti-PVR effect of fucoidan.

Results: Fucoidan reversed the transforming growth factor (TGF)-β1-induced EMT of RPE cells, including the increased expression of α-smooth muscle actin (α-SMA) and fibronectin and down-regulation of E-cadherin in human primary RPE cells. Moreover, the upregulation of phosphorylated Smad2/3 induced by TGF-β1 was suppressed by fucoidan. Fucoidan also inhibited the migration and contraction of RPE cells induced by TGF-β1. In vivo, fucoidan inhibited the progression of experimental PVR in rabbit eyes. Histological findings showed that fucoidan suppressed the formation of α-SMA-positive epiretinal membranes.

Conclusion: Our findings regarding the protective effects of fucoidan on the EMT of RPE cells and experimental PVR suggest the potential clinical application of fucoidan as an anti-PVR agent.

Keywords: Epithelial-mesenchymal transition; Fucoidan; Proliferative vitreoretinopathy; Retinal pigment epithelium.

MeSH terms

  • Actins / metabolism
  • Aldehyde Dehydrogenase 1 Family
  • Animals
  • Cadherins / metabolism
  • Cell Movement / drug effects
  • Cells, Cultured
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Eye / diagnostic imaging
  • Fibronectins / metabolism
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Neoplasm Staging
  • Phosphorylation / drug effects
  • Polysaccharides / pharmacology*
  • Polysaccharides / therapeutic use
  • Protective Agents / pharmacology*
  • Protective Agents / therapeutic use
  • Rabbits
  • Retinal Dehydrogenase / genetics
  • Retinal Dehydrogenase / metabolism*
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / metabolism
  • Smad2 Protein / metabolism
  • Smad3 Protein / metabolism
  • Tomography, Optical Coherence
  • Transforming Growth Factor beta1 / pharmacology
  • Vitreoretinopathy, Proliferative / drug therapy
  • Vitreoretinopathy, Proliferative / mortality
  • Vitreoretinopathy, Proliferative / pathology*

Substances

  • ACTA2 protein, human
  • Actins
  • Cadherins
  • Fibronectins
  • Isoenzymes
  • Polysaccharides
  • Protective Agents
  • Smad2 Protein
  • Smad3 Protein
  • Transforming Growth Factor beta1
  • fucoidan
  • Aldehyde Dehydrogenase 1 Family
  • ALDH1A1 protein, human
  • Retinal Dehydrogenase