Establishment of a multilayered 3D cellular model of the retinal-blood barrier

Int J Pharm. 2019 Dec 15:572:118811. doi: 10.1016/j.ijpharm.2019.118811. Epub 2019 Oct 31.

Abstract

Retinal disorders are leading causes of blindness. Still, treatment strategies are limited and the challenging anatomical barriers of the eye limit the evaluation and development of new therapeutics. Among these layers of barriers is the blood-retinal barrier, which separates the retina from the choroid by the Bruch's membrane. This work aimed to establish a 3D cellular model that recapitulates barrier properties of the BRB and diffusion through the vitreous, the main barriers encountered upon intravitreal injection. Several parameters were evaluated namely co-culture time of ARPE-19 and HUVECs and different biomaterial compositions of hydrogels to better mimic the human vitreous. The developed vitreous mimic has viscoelastic properties similar to human vitreous. Co-culture of human retinal and endothelial cells showed increased transepithelial resistance with longer co-culture times concomitant with reduced permeability to FITC-dextran 40 kDa. The proposed models lay the foundation of a platform for faster assessment of a large number of samples and without the use of animals.

Keywords: Blood-retinal barrier; Co-culture; In vitro retinal model; Ocular permeability; Vitreous mimic.

MeSH terms

  • Animal Testing Alternatives
  • Animals
  • Blood-Retinal Barrier / cytology*
  • Blood-Retinal Barrier / metabolism
  • Coculture Techniques
  • Dextrans / administration & dosage
  • Dextrans / pharmacokinetics
  • Endothelial Cells / cytology*
  • Endothelial Cells / metabolism
  • Fluorescein-5-isothiocyanate / administration & dosage
  • Fluorescein-5-isothiocyanate / analogs & derivatives
  • Fluorescein-5-isothiocyanate / pharmacokinetics
  • Humans
  • Intravitreal Injections
  • Models, Biological*
  • Permeability
  • Vitreous Body / metabolism

Substances

  • Dextrans
  • fluorescein isothiocyanate dextran
  • Fluorescein-5-isothiocyanate