March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Ocular Surface Failure Due to Limbal Stem Cell Deficiency (LSCD): Development of Two Efficient Animal Models
Author Affiliations & Notes
  • Sara Galindo
    Ocular Surface Group, IOBA-University of Valladolid, Valladolid, Spain
    Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valladolid, Spain
  • María Plata-Cordero
    Ocular Surface Group, IOBA-University of Valladolid, Valladolid, Spain
    Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valladolid, Spain
  • Elena Vuelta
    Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valladolid, Spain
    FCSF Tissue Bank, León, Spain
  • Javier Iglesias
    Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valladolid, Spain
    FCSF Tissue Bank, León, Spain
  • Marta Regueiro
    Veterinary School-University of León, León, Spain
  • Manuel Gonzalo-Orden
    Veterinary School-University of León, León, Spain
  • Denise Hileeto
    Ocular Surface Group, IOBA-University of Valladolid, Valladolid, Spain
    Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valladolid, Spain
  • Teresa Nieto-Miguel
    Ocular Surface Group, IOBA-University of Valladolid, Valladolid, Spain
    Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valladolid, Spain
  • Jose M. Herreras
    Ocular Surface Group, IOBA-University of Valladolid, Valladolid, Spain
    Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 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
  • Footnotes
    Commercial Relationships  Sara Galindo, None; María Plata-Cordero, None; Elena Vuelta, None; Javier Iglesias, None; Marta Regueiro, None; Manuel Gonzalo-Orden, None; Denise Hileeto, None; Teresa Nieto-Miguel, None; Jose M. Herreras, None; Margarita Calonge, None
  • Footnotes
    Support  CIBER-BBN (Instituto de Salud Carlos III); Ministry of Science and Innovation (SAF2010-14900)
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 3516. doi:
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      Sara Galindo, María Plata-Cordero, Elena Vuelta, Javier Iglesias, Marta Regueiro, Manuel Gonzalo-Orden, Denise Hileeto, Teresa Nieto-Miguel, Jose M. Herreras, Margarita Calonge; Ocular Surface Failure Due to Limbal Stem Cell Deficiency (LSCD): Development of Two Efficient Animal Models. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3516.

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Abstract

Purpose: : New animal models are necessary to test safety, tolerance, and efficacy of novel advanced therapies for Limbal Stem Cell Deficiency (LSCD). Rabbit models are commonly used due to their adequate cost-benefit. A porcine model of LSCD would be desirable, as not only the porcine eye is in general more similar to the human eye but also the porcine limbal niche has specifically been described as functionally equivalent to the human one. The aim of this work was to develop two complementary experimental models of: 1) partial LSCD in rabbit eyes to test tolerance and initial efficacy and; 2) total LSCD in pig eyes to test final and more extensive efficacy.

Methods: : After corneal epithelial debridement, a surgical 180º limbal peritomy or a 360º cryogenic limbectomy was performed in rabbits (n=6) or pigs (n=4), respectively. Corneal neovascularization, opacification and re-epithelization time were clinically scored weekly by two different researchers. Histopathology analyses at the end of follow-up (12 weeks) evaluated the degree of damage created in the limbal niche and the presence of inflammation and goblet cells (as a sign of conjuntival in-growth) in the central cornea. In the porcine model, two additional evaluations were performed: weekly corneal impression cytologies to detect goblet cells and laser scanning confocal microscopy (HRT-III Rostock Cornea Module) at end of follow-up.

Results: : Rabbit and porcine corneas developed epithelial defects, scarring, neovascularization, and opacification after 3 and 4 weeks, respectively, resembling human LSCD. Confocal microscopy (porcine model) demonstrated vascularization, inflammatory cells and goblet cells in the central cornea and complete (360º) limbal destruction, corroborated by pathology examination. Corneal impression also showed goblet cells. In the rabbit model, pathology showed complete destruction of the injured area (180º) and mild inflammation of the non-injured area.

Conclusions: : This is the first time that a porcine model of ocular surface failures due to LSCD, closely resembling the human condition has been successfully developed. Moreover, an efficient model of partial LSCD has been developed in rabbits. Preliminary studies to test safety, tolerance, and efficacy of novel therapies for the treatment of LSCD syndrome may be performed in the partial LSCD model in rabbit. Finally, the total LSCD porcine model may be used just before consideration for translation into clinical trials.

Keywords: cornea: epithelium • wound healing • regeneration 
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