MIF Inhibitor ISO-1 Protects Photoreceptors and Reduces Gliosis in Experimental Retinal Detachment

Bongsu Kim, Rania Kusibati, Tyler Heisler-Taylor, Dimosthenis Mantopoulos, Jiaxi Ding, Mohamed H. Abdel-Rahman, Abhay R. Satoskar, Jonathan P. Godbout, Sanjoy K Bhattacharya, Colleen M. Cebulla

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Photoreceptor death and retinal gliosis underlie the majority of vision threatening retinal diseases including retinal detachment (RD). Although the underlying pathobiology of vision limiting processes in RD is not fully understood, inflammation is known to play a critical role. We conducted an iTRAQ proteomic screen of up- and down-regulated proteins in a murine model of RD to identify potential targetable candidates. Macrophage migration inhibitory factor (MIF) was identified and evaluated for neurotoxic and pro-gliotic effects during RD. Systemic administration of the MIF inhibitor ISO-1 significantly blocked photoreceptor apoptosis, outer nuclear layer (ONL) thinning, and retinal gliosis. ISO-1 and MIF knockout (MIFKO) had greater accumulation of Müller glia pERK expression in the detached retina, suggesting that Müller survival pathways might underlie the neuroprotective response. Our data show the feasibility of the MIF-inhibitor ISO-1 to block pathological damage responses in retinal detachment and provide a rationale to explore MIF inhibition as a potential therapeutic option for RD.

Original languageEnglish (US)
Article number14336
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Gliosis
Retinal Detachment
Macrophage Migration-Inhibitory Factors
Retinal Diseases
Vertebrate Photoreceptor Cells
Neuroglia
Proteomics
Retina
Apoptosis
Inflammation
Proteins

ASJC Scopus subject areas

  • General

Cite this

Kim, B., Kusibati, R., Heisler-Taylor, T., Mantopoulos, D., Ding, J., Abdel-Rahman, M. H., ... Cebulla, C. M. (2017). MIF Inhibitor ISO-1 Protects Photoreceptors and Reduces Gliosis in Experimental Retinal Detachment. Scientific Reports, 7(1), [14336]. https://doi.org/10.1038/s41598-017-14298-9

MIF Inhibitor ISO-1 Protects Photoreceptors and Reduces Gliosis in Experimental Retinal Detachment. / Kim, Bongsu; Kusibati, Rania; Heisler-Taylor, Tyler; Mantopoulos, Dimosthenis; Ding, Jiaxi; Abdel-Rahman, Mohamed H.; Satoskar, Abhay R.; Godbout, Jonathan P.; Bhattacharya, Sanjoy K; Cebulla, Colleen M.

In: Scientific Reports, Vol. 7, No. 1, 14336, 01.12.2017.

Research output: Contribution to journalArticle

Kim, B, Kusibati, R, Heisler-Taylor, T, Mantopoulos, D, Ding, J, Abdel-Rahman, MH, Satoskar, AR, Godbout, JP, Bhattacharya, SK & Cebulla, CM 2017, 'MIF Inhibitor ISO-1 Protects Photoreceptors and Reduces Gliosis in Experimental Retinal Detachment', Scientific Reports, vol. 7, no. 1, 14336. https://doi.org/10.1038/s41598-017-14298-9
Kim B, Kusibati R, Heisler-Taylor T, Mantopoulos D, Ding J, Abdel-Rahman MH et al. MIF Inhibitor ISO-1 Protects Photoreceptors and Reduces Gliosis in Experimental Retinal Detachment. Scientific Reports. 2017 Dec 1;7(1). 14336. https://doi.org/10.1038/s41598-017-14298-9
Kim, Bongsu ; Kusibati, Rania ; Heisler-Taylor, Tyler ; Mantopoulos, Dimosthenis ; Ding, Jiaxi ; Abdel-Rahman, Mohamed H. ; Satoskar, Abhay R. ; Godbout, Jonathan P. ; Bhattacharya, Sanjoy K ; Cebulla, Colleen M. / MIF Inhibitor ISO-1 Protects Photoreceptors and Reduces Gliosis in Experimental Retinal Detachment. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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