July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Systemic Immunosuppression with Tacrolimus loaded osmotic pumps in a Rabbit Model for Limbal Stem Cell Transplantation
Author Affiliations & Notes
  • Alexander Händel
    Department of Ophthalmology, University of Cologne, Cologne, Germany
  • Sebastian E Siebelmann
    Department of Ophthalmology, University of Cologne, Cologne, Germany
  • Florian Wabnig
    Department of Ophthalmology, University of Cologne, Cologne, Germany
  • Tanja Ilmarinen
    Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
  • Boris Budko
    Department of Pharmacy, University of Cologne, Cologne, Germany
  • Laura Koivusalo
    Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
  • Heli Skottman
    Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
  • Claus Cursiefen
    Department of Ophthalmology, University of Cologne, Cologne, Germany
  • Björn Bachmann
    Department of Ophthalmology, University of Cologne, Cologne, Germany
  • Footnotes
    Commercial Relationships   Alexander Händel, None; Sebastian Siebelmann, None; Florian Wabnig, None; Tanja Ilmarinen, None; Boris Budko, None; Laura Koivusalo, None; Heli Skottman, None; Claus Cursiefen, None; Björn Bachmann, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4107. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Alexander Händel, Sebastian E Siebelmann, Florian Wabnig, Tanja Ilmarinen, Boris Budko, Laura Koivusalo, Heli Skottman, Claus Cursiefen, Björn Bachmann; Systemic Immunosuppression with Tacrolimus loaded osmotic pumps in a Rabbit Model for Limbal Stem Cell Transplantation. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4107.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Immunosuppression after allogenic Limbal Stem Cell Transplantation (LSCT) for Limbal Stem Cell Deficiency (LSCD) is crucial to prevent allogenic immune reactions and consecutive graft rejection. Until today there is no standardization in immunosuppression regimes neither in animal models nor in humans.

Methods : LSCD was induced in New Zealand White Rabbits by manual limbectomy and application of n-Heptanol. Human epithelial stem cells were grafted after LSCD induction. For systemic immunosuppression Alzet osmotic pumps (Cupertino, CA, USA) filled with Tacrolimus monohydrate were implanted subcutaneously into the neck fold. Before implantation the pumps were filled with Tacrolimus monohydrate dissolved in 96% ethanol, mixed with macrogolglycerol ricinoleate and then supplemented with NaCl 0.9%, which dilutes ethanol to 16%. The concentration of Tacrolimus was calculated for 80µg/kg body weight per day. In group 1 (n=4) the animals received dexamethasone 0.1 % eye drops BID but the pump wasn’t changed (pump implantation one week before LSCT). In group 2 (n=4) the animals did not receive topical steroids but the Tacrolimus loaded pumps were changed twice (one week before LSCT and the day of LSCT, first pump implantation 2 weeks before LSCT). Peripheral venous blood samples were taken to evaluate Tacrolimus levels at different time points. Animals from group 3 (n=4) were treated by local dexamethasone 0.1 % eye drops BID without any systemic immunosuppression. Corneas were analyzed histologically by H&E stainings three weeks after transplantation.

Results : In group 1 serum Tacrolimus levels decreased from 8.4 ± 6.5 µg/l (3 days after implantation) to 4.8 ± 0.5 µg/l (7 days after implantation) and further decreased below detection levels 10 days after implantation. In Group 2, Tacrolimus serum levels were stable at each time point (overall mean 4.9 ± 2.1 µg/l) and within therapeutic levels. H&E stainings revealed massive invasion of inflammatory cells in animals without sufficient systemic immunosuppression (group 1 and 3). In contrast corneas from group 2 with systemic but without local immunosuppression showed only few inflammatory cells.

Conclusions : Our results indicate that weekly renewal of Tacrolimus loaded osmotic pumps results in stable therapeutic serum levels leading to a minimal inflammation after Limbal Stem Cell Transplantation.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

×
×

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.

×