July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
ST266 maintains neuroprotective effects in experimental optic neuritis after removal of high molecular weight proteins
Author Affiliations & Notes
  • Keirnan Willett
    Ophthalmology, University of Pennsylvania, Scheie Eye Institute, Philadelphia, Pennsylvania, United States
  • Reas Sulaimankutty
    Ophthalmology, University of Pennsylvania, Scheie Eye Institute, Philadelphia, Pennsylvania, United States
  • Kimberly Dine
    Ophthalmology, University of Pennsylvania, Scheie Eye Institute, Philadelphia, Pennsylvania, United States
  • Howard Wessel
    Noveome Biotherapeutics Inc., Pittsburgh, Pennsylvania, United States
  • Larry R Brown
    Noveome Biotherapeutics Inc., Pittsburgh, Pennsylvania, United States
  • Kenneth S Shindler
    Ophthalmology, University of Pennsylvania, Scheie Eye Institute, Philadelphia, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Keirnan Willett, None; Reas Sulaimankutty, None; Kimberly Dine, None; Howard Wessel, Noveome Biotherapeutics Inc. (E), Noveome Biotherapeutics Inc. (P); 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, 2291. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Keirnan Willett, Reas Sulaimankutty, Kimberly Dine, Howard Wessel, Larry R Brown, Kenneth S Shindler; ST266 maintains neuroprotective effects in experimental optic neuritis after removal of high molecular weight proteins. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2291.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : ST266 is the biological secretome of Amnion-derived Multipotent Progenitor cells containing multiple growth factors and anti-inflammatory cytokines. Intranasally-administered ST266 prevents retinal ganglion cell (RGC) loss, reduces optic nerve inflammation and demyelination and attenuates visual dysfunction in experimental optic neuritis. However, specific components of ST266 that mediate these effects are not known. We compared ST266’s effects in experimental optic neuritis with and without the removal of large molecular weight proteins.

Methods : Large molecular weight proteins were removed from ST266 using conventional centrifugal filter units. Experimental optic neuritis was induced in the multiple sclerosis model experimental autoimmune encephalomyelitis (EAE) by immunization of 8 wk old C57/BL6J mice with myelin oligodendroglial glycoprotein peptide. Control mice were sham immunized with PBS. Mice were treated daily with 20 µL intranasal vehicle, ST266 or lower molecular weight ST266 from day 15 post-EAE induction (after onset of optic neuritis) until sacrifice at day 42. Brn3a-immunolabeled RGCs were counted in isolated retinas, and optic nerve sections were stained by H&E and luxol fast blue to assess inflammation and demyelination, respectively.

Results : Treatment of EAE mice with either ST266 or lower molecular weight ST266 significantly improved RGC survival and reduced optic nerve demyelination as compared with EAE mice treated with vehicle alone (p<0.05), with similar levels of RGC survival and myelination present in the two drug treatment groups. Treatment of EAE mice with either ST266 or lower molecular weight ST266 induced a strong trend towards reduced optic nerve inflammation as compared with EAE mice treated with vehicle alone, but this did not reach statistical significance (p=0.051 and p=0.174, respectively).

Conclusions : In the mouse EAE model, intranasal ST266 and ST266 lacking large molecular weight proteins demonstrate similar ability to attenuate experimental optic neuritis. Thus, higher molecular weight biomolecules present in ST266 may not be the key mediators of its neuroprotective effects. Isolation of specific lower molecular weight factors from ST266 in the future may help identify potential novel neuroprotective therapies.

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

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×