June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Modulation of host microenvironment by sustained growth factor delivery enhances donor RGC morphology following allotransplantation
Author Affiliations & Notes
  • Julia Oswald
    Schepens Eye Research Institute, Boston, Massachusetts, United States
  • John Hunter Masland
    Schepens Eye Research Institute, Boston, Massachusetts, United States
  • Chris Pernstich
    Cell Guidance Systems, Cambridge, United Kingdom
  • Petr Y Baranov
    Schepens Eye Research Institute, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Julia Oswald, Cell Guidance Systems (P); John Masland, None; Chris Pernstich, Cell Guidance Systems (E), Cell Guidance Systems (P); Petr Baranov, Cell Guidance Systems (P)
  • Footnotes
    Support  U24 grant NEI/NIH EY029893; Gilbert Foundation; NIH/NEI Core Grant P30EY003790
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 660. doi:
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    • Get Citation

      Julia Oswald, John Hunter Masland, Chris Pernstich, Petr Y Baranov; Modulation of host microenvironment by sustained growth factor delivery enhances donor RGC morphology following allotransplantation. Invest. Ophthalmol. Vis. Sci. 2020;61(7):660.

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

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Abstract

Purpose : Neurodegenerative diseases of the retina including AMD and Glaucoma are characterized by the gradual progression of their underlying pathology. Patients initially remain unaware of their progressive vision loss due to compensation by the brain. Contrary to other treatments, cell replacement promises to restore vision in advanced retinal disease. While work in our laboratory and others shows the feasibility of cell replacement in terms of donor cell differentiation in-vitro and delivery to the eye, vision recovery could take months if not years post-transplant, especially for RGC replacement. Neuroprotective strategies, widely tested to delay RGC degeneration at earlier stages of disease, may solve this impasse. Here, we investigate synergistic effects of delivering known neuroprotective factors in a slow release formulation with iPSC derived RGCs.

Methods : Retinal tissue was differentiated from Thy1-GFP mouse iPSC (C57Bl/6 background) over the course of 3 weeks in 3D-retinal organoids. RGCs were isolated by magnetic microbeads against CD90 at day 21 of development, Thy1-GFP+ RGCs are formulated at 20,000 cells in 2ul with or without GDNF/BDNF/CNTF-loaded polyhedrin-based particles (PODS). Mice were injected with NMDA 1 week prior to intravitreal injection of donor RGCs to cause RGC death, and subsequently received either cells alone, cells+PODS, or PODS alone. To assess host retinal function electroretinography (ERG) were performed at 6 weeks and 6 months post-transplant. Donor cell identity was confirmed prior to transplant by qPCR, Immunohistochemistry and Flow Cytometry.

Results : Thy1-GFP+ donor RGCs alone don’t rescue retinal function as assessed by ERG at 6 weeks post-transplantation in NMDA model of toxic optic neuropathy. Treatment with PODS and cells+PODS led to partial preservation of RGC function as measured by pSTR response at 6 weeks (32uV in PODS group vs 17uV in control) as well as 6 months post-transplantation. Donor RGC axon outgrowth and morphology, including entry into the optic nerve head was enhanced by PODS co-treatment, proposing a benefit of co-treatment towards cell delivery.

Conclusions : Modulation of host retinal microenvironment with slow-release growth factor cotreatment is an effective tool to improve transplantation outcome by improving donor RGC morphology and axon outgrowth.

This is a 2020 ARVO Annual Meeting abstract.

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