April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Cationized Gelatine based-Nanoparticles Loaded with Modified MUC5AC Encoding Plasmid for the Treatment of Murine Experimental Dry Eye (EDE)
Author Affiliations & Notes
  • Yolanda Diebold
    Ocular Surface Group, IOBA - University of Valladolid, Valladolid, Spain
    Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valladolid, Spain
  • Laura Contreras-Ruiz
    Ocular Surface Group, IOBA - University of Valladolid, Valladolid, Spain
    Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valladolid, Spain
  • Giovanni K. Zorzi
    Department of Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, Santiago de Compostela, Spain
  • Antonio López-García
    Ocular Surface Group, IOBA - University of Valladolid, Valladolid, Spain
    Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valladolid, Spain
  • Karyn F. Siemasko
    Biological Sciences, Allergan, Inc, Irvine, California
  • Denis Hileeto
    Ocular Surface Group, IOBA - University of Valladolid, Valladolid, Spain
  • Margarita Calonge
    Ocular Surface Group, IOBA - University of Valladolid, Valladolid, Spain
    Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valladolid, Spain
  • Michael E. Stern
    Biological Sciences, Allergan, Inc, Irvine, California
  • Begoña Seijo
    Department of Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, Santiago de Compostela, Spain
  • Alejandro Sánchez
    Department of Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, Santiago de Compostela, Spain
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 419. doi:
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      Yolanda Diebold, Laura Contreras-Ruiz, Giovanni K. Zorzi, Antonio López-García, Karyn F. Siemasko, Denis Hileeto, Margarita Calonge, Michael E. Stern, Begoña Seijo, Alejandro Sánchez; Cationized Gelatine based-Nanoparticles Loaded with Modified MUC5AC Encoding Plasmid for the Treatment of Murine Experimental Dry Eye (EDE). Invest. Ophthalmol. Vis. Sci. 2011;52(14):419.

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

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Abstract

Purpose: : To achieve an efficient in vivo transfection of MUC5AC, in order to restore its levels in an inflamed ocular surface, improving the physiological parameters associated with this condition.

Methods: : Cationized gelatin and chrondroitin sulfate-based nanoparticles (NPs) were prepared by ionotropic gelation and loaded with a plasmid coding for a modified MUC5AC protein (pMUC5AC) (P201031678). EDE was induced in C57BL/6 mice with subcutaneous scopolamine and exposure to an air draft for 10 days. 5µl of naked plasmid, blank NPs, pMUC5AC-NPs or cyclosporine A (CsA) were instilled in both eyes 4 times/day for 5 days. Control animals received no instillations. Clinical signs, corneal fluorescein staining and tear production were evaluated before and after EDE induction, and after treatment. MUC5AC expression was evaluated by real time RT-PCR. Ocular structures were processed for pathology evaluation, including goblet cell (GC) count. Two-way ANOVA was done for statistical analysis.

Results: : Expression of modified MUC5AC was significantly higher in cornea and conjunctiva of pMUC5AC-NP-treated EDE animals than that of controls. Neither ocular discomfort nor irritation was observed in vivo after NP treatment. Desiccating stress significantly increased corneal fluorescein staining and decreased tear production and GC numbers. However, corneal fluorescein staining and tear production significantly improved after pMUC5AC-NP and CsA treatment. Anterior eye segment of treated mice showed normal architecture and morphology with lack of inflammatory changes.

Conclusions: : pMUC5AC-NPs were able to induce the expression of modified MUC5AC in ocular surface tissues, to improve the integrity of corneal epithelial barrier and to increase tear production and GC numbers in dry eye mice. Thus, pMUC5AC-NPs may be a potential therapy for dry eye syndrome.

Keywords: cornea: tears/tear film/dry eye • gene transfer/gene therapy • inflammation 
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