July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Therapeutic efficacy of different routes of mesenchymal stem cell administration in corneal injury
Author Affiliations & Notes
  • Sachin Shukla
    Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
    L. V. Prasad Eye Institute, India
  • Srikant K Sahu
    Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
    L. V. Prasad Eye Institute, India
  • Sharad Mittal
    Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Elsayed Elbasiony
    Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • William Foulsham
    Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Sunil Chauhan
    Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Sachin Shukla, None; Srikant Sahu, None; Sharad Mittal, None; Elsayed Elbasiony, None; William Foulsham, None; Sunil Chauhan, None
  • Footnotes
    Support  NIH/NEI (R01EY024602); Department of Science and Technology (IFA-14-LSBM-104), Science and Engineering Research Board, Govt. of India and Indo-U.S. Science and Technology Forum (SERB Indo-U.S. Postdoctoral Fellowship 2017/159)
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4676. doi:
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    • Get Citation

      Sachin Shukla, Srikant K Sahu, Sharad Mittal, Elsayed Elbasiony, William Foulsham, Sunil Chauhan; Therapeutic efficacy of different routes of mesenchymal stem cell administration in corneal injury. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4676.

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

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Abstract

Purpose : Corneal injuries are associated with significant impairment in vision. Our previous work has shown that mesenchymal stem cells (MSCs) promote tissue repair and restore corneal transparency following injury. Here, we aim to evaluate the efficacies of local and systemic routes of MSC administration in suppressing corneal opacity and inflammation, while promoting tissue repair in a murine model of corneal injury.

Methods : MSCs were purified from the bone marrow of C57BL/6J mice and expanded using plastic adherence in vitro. Corneal injury was created by removal of the corneal epithelium and anterior stroma using Algerbrush and 0.5x106 MSCs were administered in mice through topical, subconjunctival, intraperitoneal and intravenous routes. Corneal opacity was evaluated using slit-lamp biomicroscopy; bright-field images were analyzed by ImageJ software and opacity was quantified as percentage of the total corneal area. Corneal fibrosis was evaluated by quantifying the mRNA expression of α-smooth muscle actin (α-SMA) through real-time PCR. Infiltration of CD45+ cells was evaluated using flow cytometry. Corneal structure was examined by hematoxylin and eosin staining of the cross sections of whole eyeball.

Results : Injury-induced corneal opacity was significantly reduced in mice receiving subconjunctival (13.96±3.41%, p=0.039) and intravenous (17.15±8.79%, p=0.041) MSCs, compared to untreated injured mice (51.97±10.05%). No significant reduction in corneal opacity was detected in mice receiving topical (41.07±6.13%) and intraperitoneal (36.79±9.97%) MSCs. Similarly, corneal expression of α-SMA was significantly reduced in subconjunctival (~90%, p=0.024) and intravenous (~78%, p=0.021) routes of MSC administration compared to untreated injured mice. Corneal infiltration of CD45+ cells was significantly reduced in subconjunctival (1.46±0.34%, p=0.042) and intravenous (1.51±0.4%, p=0.044) routes of MSC administration, but not in topical (3.08±0.28%, p=0.062) and intraperitoneal (3.58±0.18%, p=0.535) routes, compared to untreated group (5.09±0.24%). MSC treatment via subconjunctival and intravenous routes normalized corneal tissue structure to a greater extent than topical and intraperitoneal routes.

Conclusions : Our data suggest that subconjunctival and intravenous routes of MSC administration are the most effective in suppressing corneal opacity and inflammation, and promoting tissue repair.

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

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