July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Role of Vasoactive Intestinal Peptide in Survival of Corneal Endothelial Cells after Corneal Transplantation
Author Affiliations & Notes
  • Hamid-Reza Moein
    Ophthalmology/Immunology/neuroscience, Tufts Medical Center, Boston, Massachusetts, United States
  • Maria J Lopez
    Ophthalmology/Immunology/neuroscience, Tufts Medical Center, Boston, Massachusetts, United States
  • Aakash Gupta
    Ophthalmology/Immunology/neuroscience, Tufts Medical Center, Boston, Massachusetts, United States
  • Deshea L Harris
    Ophthalmology/Immunology/neuroscience, Tufts Medical Center, Boston, Massachusetts, United States
  • Pedram Hamrah
    Ophthalmology/Immunology/neuroscience, Tufts Medical Center, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Hamid-Reza Moein, None; Maria Lopez, None; Aakash Gupta, None; Deshea Harris, None; Pedram Hamrah, Allergan (C), Allergan (F), Dompe (C), GlaxoSmithKline (C), GlaxoSmithKline (F), Shire (C), Shire (F)
  • Footnotes
    Support  NIH R01-EY022695 (PH), NIH R21-EY025393-01(PH), EBAA/Richard Lindstrom (HM)
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 4437. doi:
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    • Get Citation

      Hamid-Reza Moein, Maria J Lopez, Aakash Gupta, Deshea L Harris, Pedram Hamrah; Role of Vasoactive Intestinal Peptide in Survival of Corneal Endothelial Cells after Corneal Transplantation. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4437.

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

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Abstract

Purpose : Corneal endothelial cell (CEC) loss is one of the major causes of corneal graft failure and can lead to loss of vision. This study tested the hypothesis that vasoactive intestinal peptide (VIP) is decreased following corneal transplantation and that VIP treatment can prevent CEC loss.

Methods : Corneal buttons from 8-week-old C57BL/6 mice were transplanted to age-and sex-matched BALB/c mice. Recipients were treated with intraperitoneal injection of PBS (control), VIP acetate salt, VIP antagonist, and methylprednisolone (MEP) 1 day prior to transplantation and then daily for 2 weeks. Corneas were evaluated clinically by slit-lamp and anterior segment OCT. Corneal VIP mRNA expression was assessed by real-time PCR. Excised whole-mount corneas were stained with fluorescent antibodies against ZO-1, CD45, and beta tubulin III to assess endothelial cell density (ECD), immune cell, and corneal nerve densities at week 2 post-transplantation, respectively.

Results : Corneal neovascularization was significantly increased in the VIP antagonist-treated as compared to MEP-treated mice (6.4±0.6 vs. 1.0±0.5; p=0.005). Central corneal thickness (CCT) was also significantly increased in the VIP antagonist-treated mice as compared to controls at week 2 post-transplantation (271.2±32.0 vs. 146.8±18.4 μm; p=0.01). VIP mRNA decreased 4.1-fold at week 1 post-transplantation (p=0.03). ECD was increased to 1152±153.5 (p=0.007) and 1099±86.5 cells/mm2 (p=0.04) in VIP- and MEP-treated groups as compared to controls (460.0±117.1), respectively. Interestingly ECD decreased with VIP antagonist as compared to the VIP-treated group (512.0±156.0 cells/mm2; p=0.02). VIP treatment increased corneal nerve density as compared to controls (18.4±1.8 vs. 10.4±1.5 mm/mm2; p=0.03) and VIP antagonist decreased nerve density to 9.4±3.3 mm/mm2 compared to VIP treatment (p=0.03). VIP treatment did not significantly change CD45+ cell density into the cornea (1255.0±211.8 cells/mm2); however, VIP antagonist increased CD45+ cell density as compared to controls (2241.0±31.3 vs. 1540.0±97.3 cells/mm2; p=0.003).

Conclusions : Exogenous VIP increases both ECD and corneal nerve density in transplanted corneal grafts. Interestingly, VIP antagonist increased CCT and immune cell infiltration to the cornea as compared to controls. Further studies are warranted to study the long-term effects of VIP on corneal graft endothelial survival.

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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