On Further Development of Barrier Modulation as a Technique for Systemic Ocular Drug Delivery

  • Finnian Hanrahan
  • Matthew Campbell
  • Anh T. Nguyen
  • Mayu Suzuki
  • Anna-Sophia Kiang
  • Lawrence C. Tam
  • Oliviero L. Gobbo
  • Sorcha Ní Dhubhghaill
  • Marian M. Humphries
  • Paul F. Kenna
  • Pete Humphries
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 723)

Abstract

Many systemically deliverable low-molecular-weight drugs with proven efficacy as neuroprotective, anti-inflammatory, anti-neovascular, cytotoxic, or anti-microbial agents are blocked from entering the eye by the inner blood-retina barrier. Recent reports from this laboratory have shown that it is possible to modulate the iBRB reversibly in mice by systemic administration of siRNA targeting transcripts derived from claudin 5, a tight junction protein of the endothelial cells lining the inner retinal microvasculature, rendering the iBRB transiently permeable to compounds up to approximately 1,000 Da in molecular weight. The system has been validated by demonstrating improved visual function in a model of autosomal recessive retinitis pigmentosa (IMPDH1−/− mice) and by suppression of light-induced damage to the retina, in each case by systemic drug delivery following barrier modulation. In this review, we explore how this technique could be improved by the down-regulation of transcripts encoding other tight junction endothelial proteins, particularly ones which would enable outer blood-retina barrier modulation.

Keywords

Blood-retinal barrier Drug delivery Tight junction Claudin-5 Barrier modulation Retinal pigmented epithelium IMPDH1 

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Finnian Hanrahan
    • 1
  • Matthew Campbell
    • 1
  • Anh T. Nguyen
    • 1
  • Mayu Suzuki
    • 1
  • Anna-Sophia Kiang
    • 1
  • Lawrence C. Tam
    • 1
  • Oliviero L. Gobbo
    • 2
  • Sorcha Ní Dhubhghaill
    • 1
  • Marian M. Humphries
    • 1
  • Paul F. Kenna
    • 1
  • Pete Humphries
    • 1
  1. 1.Ocular Genetics Unit, Smurfit Institute of GeneticsTrinity College DublinDublin 2Ireland
  2. 2.School of Pharmacy and Pharmaceutical SciencesTrinity College DublinDublin 2Ireland

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