Transient expression of Wnt5a elicits ocular features of pseudoexfoliation syndrome in mice

PLoS One. 2019 Mar 6;14(3):e0212569. doi: 10.1371/journal.pone.0212569. eCollection 2019.

Abstract

Purpose: Pseudoexfoliation (PEX) syndrome is an age-related systemic disease with ocular manifestations. The development of animal models is critical in order to elucidate the cause of the disease and to test potential treatment regimens. The purpose of this study is to report phenotypes found in mouse eyes injected with Adenovirus coding Wnt5a. Some of the phenotypes resemble those found in PEX patients while others are different.

Methods: Recombinant Adenovirus coding Wnt5a or green fluorescent protein (GFP) were injected into mouse eyes. Two months after the injection, eyes were examined for PEX phenotypes using slit lamp, fluorescence stereomicroscope, histological staining, immunostaining and transmission electron microscope.

Result: Certain ocular features of PEX syndrome were found in mouse eyes injected with recombinant Adenovirus coding Wnt5a. These features include accumulation of exfoliation-like extracellular material on surfaces of anterior segment structures and its dispersion in the anterior chamber, saw-tooth appearance and disrupted basement membrane of the posterior iris pigment epithelium, iris stromal atrophy and disorganized ciliary zonules. Ultrastructure analysis of the exfoliation material revealed that the microfibril structure found in this model was different from those of PEX patients.

Conclusion: These features, resembling signs of ocular PEX syndrome in patients, suggest that new information obtained from this study will be helpful for developing better mouse models for PEX syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Exfoliation Syndrome* / genetics
  • Exfoliation Syndrome* / metabolism
  • Exfoliation Syndrome* / pathology
  • Female
  • Humans
  • Lens, Crystalline* / metabolism
  • Lens, Crystalline* / ultrastructure
  • Male
  • Mice
  • Mice, Transgenic
  • Retinal Pigment Epithelium* / metabolism
  • Retinal Pigment Epithelium* / ultrastructure
  • Wnt-5a Protein* / biosynthesis
  • Wnt-5a Protein* / genetics

Substances

  • Wnt-5a Protein
  • Wnt5a protein, mouse

Grants and funding

This work was supported in part by grants from The Glaucoma Foundation (YY), EY011845 and Ohio Lions Eye Research Foundation (WWK), and the Henry M. Cohn Glaucoma Research Fund of the New York Eye and Ear Infirmary of Mount Sinai (RR).