July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Efficacy of alpha-Melanocyte Stimulating Hormone (α-MSH) in Improving Corneal Endothelial Cell Viability and Allograft Survival in High-Risk Murine Corneal Transplantation
Author Affiliations & Notes
  • ZHONGMOU SUN
    Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
  • Zala Luznik
    Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
  • Takeshi Nakao
    Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
  • Ahmad Kheirkhah
    Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
  • Ula V Jurkunas
    Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
  • Reza Dana
    Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   ZHONGMOU SUN, None; Zala Luznik, None; Takeshi Nakao, None; Ahmad Kheirkhah, None; Ula Jurkunas, None; Reza Dana, None
  • Footnotes
    Support  NIH R21 EY029387, Eye Bank Association of America Richard Lindstrom Research Grant
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3824. doi:
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      ZHONGMOU SUN, Zala Luznik, Takeshi Nakao, Ahmad Kheirkhah, Ula V Jurkunas, Reza Dana; Efficacy of alpha-Melanocyte Stimulating Hormone (α-MSH) in Improving Corneal Endothelial Cell Viability and Allograft Survival in High-Risk Murine Corneal Transplantation. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3824.

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

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Abstract

Purpose : The success of corneal transplantation relies largely on the integrity of corneal endothelial cells (CEnCs). Even in the absence of acute graft rejection, there is a continuous loss of CEnC after transplantation. Very little is known about the effects of nerve-derived factors on CEnC integrity and allograft outcomes. Here, we investigated the effect α-MSH on CEnC viability and corneal allograft survival using a mouse model of high-risk corneal transplantation.

Methods : Murine corneal cups (n=5/group) were incubated in the presence of interferon-gamma (IFN-γ; 60 ng/ml) to induce CEnC apoptosis with or without α-MSH (10-4 M) for 18 hours. TUNEL staining was used to quantify CEnC apoptosis and corneas were evaluated using confocal microscopy. High-risk graft beds were induced by placing intrastromal sutures in the corneas of six-week-old BALB/c recipient mice two weeks prior to performing allogeneic corneal transplantation using C57BL/6 donor mice. Graft recipients were treated with subconjunctival injection of α-MSH (10-4 M) or PBS (as the control) biweekly for eight weeks (n=7/group). Corneal thickness, opacity and neovascularization scores were measured weekly using optical coherence tomography (OCT) and slit lamp imaging.

Results : Corneal cups treated with α-MSH had significantly lower percentage of apoptotic CEnCs (1.2±1.3%) compared to the control group (14.2±8.8%) (p=0.008). None of the transplants in the control group survived by week 6, while 43% of the transplants in the α-MSH treated group survived by week 8 after transplantation (Log-rank test; p=0.0129). Corneal opacity scores were significantly lower in the α-MSH treated group (2.86±0.34) compared to the control group (3.57±0.19) at week 6 (p=0.048). However, no significant differences were observed in the corneal thickness (254±41 µm in the α-MSH treated group vs. 265±38 µm in the control group; p=0.43) or in the neo-vascularization score (7±0.72 in the α-MSH treated group vs. 7.14±0.43 in the control group; p=0.42) between the two groups.

Conclusions : These findings indicate that α-MSH exerts a protective effect on CEnC and improves corneal allograft survival in the high-risk setting.

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

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