July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Suppression of Experimental Optic Neuritis and Myelitis by Amnion-derived Multipotent Progenitor Cells
Author Affiliations & Notes
  • Reas Sulaimankutty
    Univ of Pennsylvania, Scheie Eye Inst, Philadelphia, Pennsylvania, United States
  • Kimberly Dine
    Univ of Pennsylvania, Scheie Eye Inst, Philadelphia, Pennsylvania, United States
  • Ahmara Ross
    Univ of Pennsylvania, Scheie Eye Inst, Philadelphia, Pennsylvania, United States
  • Keirnan Willett
    Univ of Pennsylvania, Scheie Eye Inst, Philadelphia, Pennsylvania, United States
  • Rick Banas
    Noveome Biotherapeutics, Inc.,, Pittsburgh, Pennsylvania, United States
  • Larry R Brown
    Noveome Biotherapeutics, Inc.,, Pittsburgh, Pennsylvania, United States
  • Kenneth S Shindler
    Univ of Pennsylvania, Scheie Eye Inst, Philadelphia, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Reas Sulaimankutty, None; Kimberly Dine, None; Ahmara Ross, None; Keirnan Willett, None; Rick Banas, Noveome Biotherapeutics, Inc., (E); Larry Brown, Noveome Biotherapeutics, Inc., (E), Noveome Biotherapeutics, Inc., (P); Kenneth Shindler, Noveome Biotherapeutics, Inc., (F), Noveome Biotherapeutics, Inc., (C)
  • Footnotes
    Support  NIH Grant EY019014; Research to Prevent Blindness; the F. M. Kirby Foundation: and Noveome Biotherapeutics, Inc.
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2288. doi:https://doi.org/
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      Reas Sulaimankutty, Kimberly Dine, Ahmara Ross, Keirnan Willett, Rick Banas, Larry R Brown, Kenneth S Shindler; Suppression of Experimental Optic Neuritis and Myelitis by Amnion-derived Multipotent Progenitor Cells. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2288. doi: https://doi.org/.

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

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Abstract

Purpose : ST266 is the biological secretome of Amnion-derived Multipotent Progenitor (AMP) cells. ST266 proteins accumulate in eyes and optic nerves following intranasal delivery, resulting in selective suppression of optic neuritis in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, without suppressing spinal cord lesions. We tested the hypothesis that systemic AMP cell administration could suppress both optic neuritis and myelitis in EAE.

Methods : C57/BL6 EAE mice, induced by immunization with myelin oligodendroglial glycoprotein peptide, were administered 2x106 AMP cells, or were sham-injected, by either intravenous or intraperitoneal injection on day 9 after EAE induction. Additional mice received repeated administrations of 1x106 AMP cells on days 9, 12, and 15. Spinal cord dysfunction was assessed by daily scoring of EAE-induced ascending paralysis, and visual function was assessed by optokinetic responses weekly until sacrifice 6 weeks post-immunization. Retinal ganglion cells (RGCs) were immunolabeled with Brn3a antibodies and counted. Inflammation was assessed by H&E and Iba1 staining, and demyelination by luxol fast blue staining, of spinal cord and optic nerve sections.

Results : Single high-dose intravenous and intraperitoneal, and repeated low-dose intravenous, administration of AMP cells significantly reduced ascending paralysis in EAE mice (p<0.001). Repeated low-dose intravenous and intraperitoneal AMP cell administration significantly attenuated visual dysfunction in EAE mice (p<0.05). All four AMP cell treatment cohorts demonstrated increased RGC survival (p<0.05) and decreased optic nerve inflammation (p<0.05) as compared with sham-treated EAE mice, and AMP cells induced variable levels of improvement in optic nerve demyelination and spinal cord inflammation and demyelination.

Conclusions : Systemic AMP cell administration inhibits RGC loss and reduces visual dysfunction induced by EAE optic neuritis, similar to previously demonstrated effects of intranasally-delivered ST266. Importantly, AMP cells also promote neuroprotective effects in EAE spinal cords, marked by reduced paralysis. Further investigation of AMP cells as a potential therapy for inflammatory demyelinating disease is warranted.

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

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