May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Ocular Toxicity and Distribution of Intravitreal and Subconjunctival Rapamycin in Horses
Author Affiliations & Notes
  • J. H. Salmon
    Clinical Sciences, North Carolina State University, Raleigh, North Carolina
  • L. C. Douglas
    Clinical Sciences, North Carolina State University, Raleigh, North Carolina
  • N. Yi
    Clinical Sciences, North Carolina State University, Raleigh, North Carolina
  • J. L. Davis
    Clinical Sciences, North Carolina State University, Raleigh, North Carolina
  • B. C. Gilger
    Clinical Sciences, North Carolina State University, Raleigh, North Carolina
  • Footnotes
    Commercial Relationships  J.H. Salmon, None; L.C. Douglas, None; N. Yi, None; J.L. Davis, None; B.C. Gilger, None.
  • Footnotes
    Support  The Merck-Merial Veterinary Scholars Research Foundation, NCSU Equine Uveitis Research Fund, State of North Carolina
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3611. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      J. H. Salmon, L. C. Douglas, N. Yi, J. L. Davis, B. C. Gilger; Ocular Toxicity and Distribution of Intravitreal and Subconjunctival Rapamycin in Horses. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3611. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: : Rapamycin (RAPA) is a potent T-cell inhibitor that has been shown to reduce ocular inflammation in uveitis. The purpose of this study was to evaluate the in vitro release rate and photosensitivity of RAPA and to determine the ocular toxicity and distribution of intravitreal and subconjunctival RAPA as a possible treatment for equine recurrent uveitis, a common naturally occurring uveitis in horses.

Methods: : 2.5 mg, 5 mg, and 10 mg of RAPA were placed in 10 ml of PBS and maintained in a water bath at 37 C. Two vials of PBS alone served as controls. Vials were either wrapped in foil or subjected to room light. Samples were taken daily for 14 days, biweekly for 2 weeks, and weekly for 3 months and RAPA levels determined by HPLC. Six normal adult horses received either 5 mg or 10 mg of drug intravitreally or 10 mg of drug subconjunctivally in one eye. The contralateral eye received 1 ml of PEG-400 either intravitreally or subconjunctivally. Complete ophthalmic exams and scotopic ERG were performed prior to injection and on days 1, 7, 14, and 21 post-injection. The eyes were enucleated and samples were collected for RAPA concentrations and histopathology.

Results: : The in vitro samples showed no difference in light vs. dark RAPA concentrations. Ocular injections were well tolerated with only one horse developing subconjunctival hemorrhage. No visual or ocular changes were noted on ophthalmic examination or histopathology. RAPA was not detected intraocularly in eyes receiving subconjunctival 10 mg RAPA. Both the 5 mg and 10 mg intravitreal injections had aqueous humor levels at 7 days after injection; however, only eyes receiving 10 mg had detectable vitreal levels of drug at 21 days post-injection.

Conclusions: : No evidence of RAPA phototoxicity was observed. There was no evidence of ocular toxicity of up to 10 mg of RAPA in PEG-400 injected subconjunctivally or intravitreally in normal equine eyes. Subconjunctival injection of RAPA may not provide therapeutic intraocular concentrations. Further study is needed to determine efficacy of intravitreal RAPA as a treatment for uveitis.

Keywords: uveitis-clinical/animal model • drug toxicity/drug effects • injection 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×