June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Neuroprotective and anti-gliotic effects of MIF Inhibitor ISO-1 in experimental murine retinal detachment
Author Affiliations & Notes
  • Colleen M Cebulla
    Havener Eye Institute, Ophthalmology and Visual Science, The Ohio State University, Columbus, Ohio, United States
  • Bongsu Kim
    Havener Eye Institute, Ophthalmology and Visual Science, The Ohio State University, Columbus, Ohio, United States
  • Rania Kusibati
    Havener Eye Institute, Ophthalmology and Visual Science, The Ohio State University, Columbus, Ohio, United States
  • Tyler Heisler-Taylor
    Havener Eye Institute, Ophthalmology and Visual Science, The Ohio State University, Columbus, Ohio, United States
  • Dimosthenis Mantopoulos
    Havener Eye Institute, Ophthalmology and Visual Science, The Ohio State University, Columbus, Ohio, United States
  • Jiaxi Ding
    Havener Eye Institute, Ophthalmology and Visual Science, The Ohio State University, Columbus, Ohio, United States
  • Abhay Satoskar
    Division of Experimental Pathology, The Ohio State University, Columbus, Ohio, United States
  • Jonathan P. Godbout
    Department of Neuroscience, The Ohio State University, Columbus, Ohio, United States
  • Sanjoy K Bhattacharya
    Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States
  • Mohamed H. Abdel-Rahman
    Havener Eye Institute, Ophthalmology and Visual Science, The Ohio State University, Columbus, Ohio, United States
    Division Human Genetics, The Ohio State University, Columbus, Ohio, United States
  • Footnotes
    Commercial Relationships   Colleen Cebulla, None; Bongsu Kim, None; Rania Kusibati, None; Tyler Heisler-Taylor, None; Dimosthenis Mantopoulos, None; Jiaxi Ding, None; Abhay Satoskar, None; Jonathan Godbout, None; Sanjoy Bhattacharya, None; Mohamed Abdel-Rahman, None
  • Footnotes
    Support  NIH K08EY022672, P30 CA016058 ( OSU-CCC Nucleic Acids Shared Resource), NCATS KL2TR001068. EY014801 (core grant of BPEI). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding institutions. Additional funds were provided by the Ohio Lions Eye Research Foundation, Ophthalmology Fund #313310, and the Patti Blow Fund
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5969. doi:
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    • Get Citation

      Colleen M Cebulla, Bongsu Kim, Rania Kusibati, Tyler Heisler-Taylor, Dimosthenis Mantopoulos, Jiaxi Ding, Abhay Satoskar, Jonathan P. Godbout, Sanjoy K Bhattacharya, Mohamed H. Abdel-Rahman; Neuroprotective and anti-gliotic effects of MIF Inhibitor ISO-1 in experimental murine retinal detachment. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5969.

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

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Abstract

Purpose : Pro-inflammatory factors promote retinal gliosis and photoreceptor death that underlie vision-threatening complications of retinal detachment (RD). The purpose of this study is to test the hypothesis that inhibition of the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) blocks photoreceptor apoptosis and retinal gliosis in RD.

Methods : RDs were induced by subretinal injection of hyaluronic acid into left eyes of (16-24 week-old) C57BL/6 female mice (n=6-18/group) or BALB/c Mif knockout mice and background controls (n=10/group) under an IACUC-approved protocol. Fellow eyes served as controls. Eyes were enucleated and processed for immunofluorescence and TUNEL analysis. Retinas were isolated for RNA or protein extraction. 8-plex iTRAQ labeled proteomics was performed to evaluated up- and down-regulated proteins in RD compared to controls. ELISA evaluated MIF expression. C57BL/6 mice were treated with daily intraperitoneal injection of MIF inhibitor ISO-1 or vehicle and retinas were evaluated for apoptosis, inflammatory infiltrate, and gliosis.

Results : MIF was up-regulated 1.9-fold in RDs on iTRAQ analysis, which was further corroborated by ELISA (1.7 ± 0.079 ng MIF/µg total protein in controls vs. 1.87±0.138 in RD, *p≤0.089). Upregulated MIF was also detected in subretinal macrophages in RD. ISO-1 (40mg/kg) significantly decreased TUNEL positive photoreceptors in RD ((4125.89 ± 849.5 cells/mm2 retina vehicle vs 588.68 ± 409.5 cells/mm2 retina ISO-1, p=0.003). The density and polarization of macrophages were not altered. Retinal gliosis GFAP expression was reduced by ISO-1 treatment and MIF genetic depletion. Retinal phosphorylated ERK levels were increased in ISO-1 and MIF genetic depletion.

Conclusions : MIF inhibition should be explored as a potential therapeutic adjunct for RD.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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