April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Cell Therapy Of Alkali Burned Cornea With Human Umbilical Mesenchymal Stem Cells In The Mouse Model
Author Affiliations & Notes
  • Hongshan Liu
    Ophthalmology, University of Cincinnati, Cincinnati, Ohio
  • Jianhua Zhang
    Ophthalmology, University of Cincinnati, Cincinnati, Ohio
  • Yong Yuan
    Ophthalmology, University of Cincinnati, Cincinnati, Ohio
  • Martin Sieber
    Bionet Corp., Taiwan, Taiwan
  • Chia-Yang Liu
    Ophthalmology, University of Cincinnati, Cincinnati, Ohio
  • Winston W.-Y. Kao
    Ophthalmology, University of Cincinnati, Cincinnati, Ohio
  • Footnotes
    Commercial Relationships  Hongshan Liu, None; Jianhua Zhang, None; Yong Yuan, None; Martin Sieber, None; Chia-Yang Liu, None; Winston W.-Y. Kao, None
  • Footnotes
    Support  Grants NIH/NEI EY011845 & EY013755, Research to Prevent Blindness and Ohio Lions Eye Research Foundation
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 3944. doi:
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      Hongshan Liu, Jianhua Zhang, Yong Yuan, Martin Sieber, Chia-Yang Liu, Winston W.-Y. Kao; Cell Therapy Of Alkali Burned Cornea With Human Umbilical Mesenchymal Stem Cells In The Mouse Model. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3944.

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

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Abstract

Purpose: : Corneal alkali burn, one of the most intractable ocular disorders, causes severe tissue damage, persistent inflammation, and loss of vision. Transplantation of umbilical mesenchymal stem cells (UMSC) suppresses host immune responses and inflammation. Herein, we examined the efficacy of UMSC transplantation in the restoration of corneal transparency after alkali burn.

Methods: : UMSC were labeled by DiI in vitro, and then intrastromally transplanted into alkali-burned mouse cornea after 24 hours of injury. The healing of burned corneas was evaluated by in vivo confocal microscopy with HRTII (Heidelberg Retina Tomography II). Immunostaining was used to detect inflammatory cell types and the phenotypes of UMSC-derived cells; TUNEL analysis was applied to determine the apoptosis; and the second harmonic generation (SHG) was employed to access the structure of stromal collagen fibers.

Results: : In UMSC-transplanted corneas, HRTII examination revealed a low corneal haze similar to normal cornea; furthermore, the image of forward and back light scatter of SHG displayed a regular collagen fiber structure with flat and parallel stromal lamellae. In contrast, PBS-injected cornea displayed severe corneal stromal haze and irregular arrangement of stromal collagen fibers. Immunostaining verified severe inflammation characterized by the presence of CD45, CD11b, CD90, and F4/80-positive cells in PBS treated cornea and very little inflammatory cells were found in UMSC transplanted corneas. TUNEL analysis showed a large number of apoptotic stromal cells in injured corneas treated with PBS, but very few were found in corneas receiving UMSC. Transplanted UMSC assume a phenotype of keratocytes, e.g., dendritic morphology, expression of corneal unique keratocan and lumican, and CD34. Immunostaining did not detect the presence of IDO, iNOS, TSG6; only PTX3 was detected in UMSC-derived cells at 72 h after transplantation. Treatment with recombinant PTX3 protein via intrastromal injection significantly decreased corneal haze and infiltration of inflammatory cells.

Conclusions: : UMSC transplantation can suppress inflammation and stromal cell apoptosis in alkali-burned mouse corneas. Our results suggest that UMSC transplantation is an effective treatment of alkali burned cornea.

Keywords: cornea: basic science • trauma • wound healing 
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