April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Transscleral Permeability of Tauroursodeoxycholic Acid
Author Affiliations & Notes
  • J. H. Boatright
    Ophthalmology, Emory University School of Med, Atlanta, Georgia
  • S. S. Sidney
    Ophthalmology, Emory University School of Med, Atlanta, Georgia
  • E. S. Kim
    Ophthalmology, Emory University School of Med, Atlanta, Georgia
  • J. M. Nickerson
    Ophthalmology, Emory University School of Med, Atlanta, Georgia
  • H. F. Edelhauser
    Ophthalmology, Emory University School of Med, Atlanta, Georgia
  • Footnotes
    Commercial Relationships  J.H. Boatright, SMG Therapeutics, P; ORA, R; S.S. Sidney, None; E.S. Kim, None; J.M. Nickerson, SMG Therapeutics, P; H.F. Edelhauser, None.
  • Footnotes
    Support  Abraham J. & Phyllis Katz Foundation, Foundation Fighting Blindness, Research to Prevent Blindness, NIH Grants R01EY014026, R01EY016470, R24-EY017045, and P30EY06360
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 5958. doi:
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    • Get Citation

      J. H. Boatright, S. S. Sidney, E. S. Kim, J. M. Nickerson, H. F. Edelhauser; Transscleral Permeability of Tauroursodeoxycholic Acid. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5958.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Systemic injections of the hydrophilic bile acid tauroursodeoxycholic acid (TUDCA) slow retina degeneration in genetic and light damage rodent models of blindness. As eventual use in humans may require ocular delivery, in the current work we assessed whether TUDCA in Balanced Salt Solution (BSS) or Balanced Salt Solution Plus (BSS+) can diffuse across human donor sclera.

Methods: : Human donor sclera was mounted in a Lucite block perfusion chamber. The outer surface of the sclera was exposed to 500 µl of TUDCA (50 mg/ml) in either BSS or BSS+ for 24 hours. Perfusate fractions were collected every 2 hrs over a 24 hr period. Ultra performance liquid chromatography (UPLC)/tandem mass spectrometry (MSn) was used to quantitate TUDCA and uncongugated ursodeoxycholic acid (UDCA) in perfusates. The MS was tuned to specifically detect TUDCA, UDCA, and UDCAd4 (a deuterated form of UDCA used for quantitating TUDCA and UDCA).

Results: : The ion transitions for TUDCA and UDCA were 517.2 (parent ion) > 464.1 (primary daughter ion), UDCA 410.2 (parent ion) > 357.2 (primary daughter ion), respectively. TUDCA readily diffused across the sclera. The transscleral permeability constant (Kconst) for TUDCA was 1.37 x 10-6 cm/sec in BSS and 1.75 x 10-6 cm/sec in BSS+.

Conclusions: : TUDCA readily diffuses across human cadaver scleral tissue. It may be that TUDCA can be therapeutically delivered via transscleral routes without the sclera acting as a major barrier.

Keywords: neuroprotection • sclera • drug toxicity/drug effects 

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