Retinoic acid suppresses the adhesion and migration of human retinal pigment epithelial cells

Exp Eye Res. 2013 Apr:109:22-30. doi: 10.1016/j.exer.2013.01.006. Epub 2013 Feb 19.

Abstract

The study was designed to better understand how retinoic acid (RA) influenced the migration and invasion abilities of retinal pigment epithelial cells (RPE) in vitro and how the related genes of the extracellular matrix (ECM) were expressed. The inhibition effects of RA on proliferative vitreoretinopathy (PVR) formation induced by RPE cells were studied in rabbits. Wound healing and Boyden chamber assays were used to show the abilities of migration and invasion of RPE. Microarray, real-time quantitative PCR (qPCR) and Western blotting showed how RA regulated the ECM genes. RA (10(-5) M) significantly (P < 0.05) inhibited PVR membrane and traction retinal detachment formation (80%). Moreover, RA treatment significantly inhibited the migration (80%) and invasion (65%) behaviors of human RPE cells (P < 0.05) by wound healing and Boyden chamber assays, respectively. Microarray and q PCR analysis showed RA treatment did inhibit the motility of human RPE cells by inhibition of metalloproteinases (MMP) 1, 2, 9, fibronectin-1, transforming growth factor beta, thrombospondin-1, tenascin C, most collagen, integrin, laminin molecules and along enhancing E-cadherin and MMP3 genes expression. And Western blotting indicated the coincident results on protein level of MMP1, 2, 3, 9, 14; fibronectin-1; integrinαM, β2 and E-cadherin. In conclusions, RA is a vital drug to inhibit the abilities of migration and invasion of RPE and to hamper the PVR formation by regulating some genes expression of ECM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Cell Adhesion / drug effects*
  • Cell Adhesion / physiology
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Movement / drug effects*
  • Cell Movement / physiology
  • Cells, Cultured
  • Cytoskeleton / drug effects
  • Cytoskeleton / physiology
  • Disease Models, Animal
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / physiology
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / metabolism
  • Rabbits
  • Retinal Pigment Epithelium / cytology*
  • Retinal Pigment Epithelium / drug effects*
  • Retinal Pigment Epithelium / physiology
  • Tretinoin / metabolism
  • Tretinoin / pharmacology*
  • Vitreoretinopathy, Proliferative / drug therapy*
  • Vitreoretinopathy, Proliferative / pathology
  • Vitreoretinopathy, Proliferative / physiopathology
  • Wound Healing / drug effects
  • Wound Healing / physiology

Substances

  • Antineoplastic Agents
  • Cell Adhesion Molecules
  • Extracellular Matrix Proteins
  • RNA, Messenger
  • Tretinoin