July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
The Effect of Cultured Autologous Oral Mucosal Epithelial Cell Sheet (CAOMECS) Graft on Corneas
with Limbal Stem Cell Deficiency and Neovascularization
Author Affiliations & Notes
  • Fawzia Bardag-Gorce
    Hematology, LA BioMed at Harbor UCLA Medical Center, Torrance, California, United States
  • Richard Hoft
    Ophthalmology at Harbor-UCLA medical Center, LA BioMed , Torrance, California, United States
  • Derek Pan
    Hematology, LA BioMed at Harbor UCLA Medical Center, Torrance, California, United States
  • Kavita Narwani
    Hematology, LA BioMed at Harbor UCLA Medical Center, Torrance, California, United States
  • Michael Di Lorenzo
    Hematology, LA BioMed at Harbor UCLA Medical Center, Torrance, California, United States
  • Daileen Cortez
    Hematology, LA BioMed at Harbor UCLA Medical Center, Torrance, California, United States
  • Joan Oliva
    Hematology, LA BioMed at Harbor UCLA Medical Center, Torrance, California, United States
  • Yutaka Niihara
    Hematology, LA BioMed at Harbor UCLA Medical Center, Torrance, California, United States
  • Footnotes
    Commercial Relationships   Fawzia Bardag-Gorce, None; Richard Hoft, None; Derek Pan, None; Kavita Narwani, None; Michael Di Lorenzo, None; Daileen Cortez, None; Joan Oliva, None; Yutaka Niihara, Emmaus Life Sciences (F)
  • Footnotes
    Support  Emmaus Life Sciences Inc.
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3868. doi:
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      Fawzia Bardag-Gorce, Richard Hoft, Derek Pan, Kavita Narwani, Michael Di Lorenzo, Daileen Cortez, Joan Oliva, Yutaka Niihara; The Effect of Cultured Autologous Oral Mucosal Epithelial Cell Sheet (CAOMECS) Graft on Corneas
      with Limbal Stem Cell Deficiency and Neovascularization. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3868.

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

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Abstract

Purpose : The primary clinical manifestations of limbal stem cell deficiency (LSCD) are epithelial defects, corneal conjunctivalization and corneal neovascularization (NV). Current treatment of corneal NV is based on the inhibition of vascular endothelial growth factor (VEGF) -- a downstream regulator of hypoxia-inducible factor (HIF). In a previous study, we have shown that cultured autologous oral mucosal epithelial cell sheet (CAOMECS) graft, engineered to reconstruct the ocular surface of a model of rabbit with LSCD, significantly decreased NV. However, the mechanism of action of CAOMECS in reducing LSCD-induced neovascularization is not fully understood. We hypothesize that CAOMECS graft decreases the activity of HIF alpha, which, in turn, results in a decrease of VEGF expression.

Methods : The study was performed on rabbits who underwent surgical limbectomy to create LSCD. CAOMECS was then grafted onto corneas to reduce the severity of LSCD and improve the ocular surface. Using immunofluorescent staining, VEGF expression was analyzed in corneal tissue sections from LSCD-diseased and from CAOMECS-grafted rabbits. Oral mucosal epithelial cells were cultured and treated with proteasome inhibitor to analyze HIF alpha and VEGF levels.

Results : Corneal neovascularization developed in rabbits with LSCD as early as 1 month after limbectomy, and was stable for at least 3 months. As previously reported (Bardag-Gorce et al. 2015), CAOMECS grafting resulted in a significant reduction of NV, and in a recovery of proteasome expression, when compared to corneas without CAOMECS grafting. VEGF expression was elevated in LSCD un-grafted corneas. VEGF expression was significantly decreased in CAOMECS grafted corneas. There was an increase in HIF alpha levels after 24 hours of proteasome inhibition in cultured oral mucosal epithelial cells.

Conclusions : CAOMECS grafting reduced corneal vascularization in our rabbit model of LSCD. The mechanism of action might be that CAOMECS grafting seeded healthy epithelial cells that contained a functional proteasome, preventing HIF alpha signaling, and thus reducing the expression of VEGF in the ocular surface.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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