Effect of retinoic acid on the tight junctions of the retinal pigment epithelium-choroid complex of guinea pigs with lens-induced myopia in vivo

Int J Mol Med. 2014 Apr;33(4):825-32. doi: 10.3892/ijmm.2014.1651. Epub 2014 Feb 10.

Abstract

Zonula occludens-1 (ZO-1) and occludin are important tight junction (TJ)-associated proteins, which are expressed in the retinal pigment epithelium (RPE)-choroid complex. Retinoic acid (RA) is a regulator of eye growth and may play an important role in forming functional TJs. The aim of this study was to detect the changes that occur in the expression of ZO-1 and occludin in the RPE-choroid complex of guinea pigs with lens-induced myopia (LIM), and to investigate the effect of RA on TJ-associated proteins in vivo. We developed an animal model of myopia by placing a -6.00 D negative lens on the right eyes of 3-week-old guinea pigs. The refractive error and axial length of the eye were measured on days 0, 3, 7 and 14. High-performance liquid chromatography (HPLC) was performed to detect the changes in endogenous RA in the RPE-choroid complex. The expression of ZO-1 and occludin was observed by immunofluorescence and assayed by western blot analysis. Additionally, 2 µl LE540 (2.5 µg/µl), an antagonist of RA receptors (RARs), was injected into the vitreous chamber of the eyes of guinea pigs with LIM and 2 µl phosphate-buffered saline (PBS) (2.5 µg/µl) were injected as a negative control. We observed no obvious change in RA, ZO-1 and occludin expression in the normal control group within 14 days. In the LIM and LIM plus PBS groups, the level of RA and the expression of ZO-1 and occludin in the RPE-choroid complex significantly increased within 14 days along with the development of myopia. However, the level of RA was inhibited and the expression of TJ-associated proteins decreased in the eyes of guinea pigs with LIM following the injection of LE540. Thus, we consider that the expression of ZO-1 and occludin is increased in the RPE-choroid complex during the development of myopia. This change in expression may be regulated by RA, a factor known to be involved in the regulation of eye growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Choroid / drug effects
  • Choroid / pathology*
  • Choroid / physiopathology
  • Disease Models, Animal
  • Fluorescent Antibody Technique
  • Guinea Pigs
  • Lens, Crystalline / drug effects
  • Lens, Crystalline / pathology*
  • Myopia / pathology*
  • Myopia / physiopathology
  • Refractometry
  • Retinal Pigment Epithelium / drug effects
  • Retinal Pigment Epithelium / pathology*
  • Retinal Pigment Epithelium / physiopathology
  • Tight Junction Proteins / metabolism
  • Tight Junctions / drug effects
  • Tight Junctions / metabolism*
  • Tretinoin / pharmacology*
  • Vision, Ocular / drug effects

Substances

  • Tight Junction Proteins
  • Tretinoin