July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
The combination of biologic-loaded liposomes and retinal ganglion cell transplant rescues retinal function in an NMDA toxicity model
Author Affiliations & Notes
  • Anne Zebitz Zebitz Eriksen
    Department of Micro- and Nanotechnology, Technical Universety of Denmark, Kgs. Lyngby, Denmark
  • Julia Oswald
    Massachusetts Eye and Ear, an affiliate of Harvard Medical School, Schepens Eye Research Institute, Boston, Massachusetts, United States
  • Paul J Kempen
    Department of Micro- and Nanotechnology, Technical Universety of Denmark, Kgs. Lyngby, Denmark
  • Fredrik Melander
    Department of Micro- and Nanotechnology, Technical Universety of Denmark, Kgs. Lyngby, Denmark
  • Michael Young
    Massachusetts Eye and Ear, an affiliate of Harvard Medical School, Schepens Eye Research Institute, Boston, Massachusetts, United States
  • Petr Y Baranov
    Massachusetts Eye and Ear, an affiliate of Harvard Medical School, Schepens Eye Research Institute, Boston, Massachusetts, United States
  • Andrew J Urquhart
    Department of Micro- and Nanotechnology, Technical Universety of Denmark, Kgs. Lyngby, Denmark
  • Footnotes
    Commercial Relationships   Anne Zebitz Eriksen, None; Julia Oswald, None; Paul Kempen, None; Fredrik Melander, None; Michael Young, None; Petr Baranov, None; Andrew Urquhart, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1706. doi:
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      Anne Zebitz Zebitz Eriksen, Julia Oswald, Paul J Kempen, Fredrik Melander, Michael Young, Petr Y Baranov, Andrew J Urquhart; The combination of biologic-loaded liposomes and retinal ganglion cell transplant rescues retinal function in an NMDA toxicity model. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1706.

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

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Abstract

Purpose : Optic neuropathies are a leading cause of blindness, with irreversible loss of retinal ganglion cells (RGCs) being the common pathology. Direct delivery or overexpression of neuroprotective growth factors and cell transplantation has shown promise in retina neuroprotection. To combine these two approaches, we have designed and tested multiloaded liposomes for simultaneous delivery of four signaling molecules with known neuroprotective properties.

Methods : Two liposomal formulations were prepared with membrane bound osteopontin peptide and one of two different PTEN-inhibitory peptides. Growth factors (IGF-1 and CNTF) were loaded in the liposome core. Cell uptake was tested in vitrousing retinal organoids, differentiated from mouse embryonic stem cells. The effect of liposomes on donor RGC survival was tested in an NMDA model of RGC loss. Empty liposomes served as control. We also injected liposomes alone to look for additive effects of the two treatments. RGCs for transplantation (tRGCs) were differentiated from Thy1-GFP iPSc. Retinal structure, function and tRGC engraftment were evaluated 4 weeks after NMDA injection.

Results : The biological activity of the liposome cargowas confirmedinHEK293Tcells, mTOR pathway was upregulated 24 hours afterliposome treatment. The liposomes were equally taken in by all retinal cell types; RGC, photoreceptors, RPE and Muller glia,however,Lip 1 showed higher uptake in all cell types tested (Figure 1). Uptake level correlated with the in vivoneuroprotective effect. Lip 1inducedsignificant preservation of host RGC number and function (1.5 fold increase in surviving RGCs, DSTR Figure 2). Although a significant effect of the liposomes on tRGCsurvivalwas not observed, there was a significant synergisticeffect of Lip 1and tRGCson retinal ganglion layer function as detected by STR.

Conclusions : We were able to effectively load liposomes with four signaling molecules that remain biologically active. The neuroprotective effect of liposomes on RGC structure and function correlated with the liposome uptake. The synergistic effect of neuroprotection and cell transplantation warrants further exploration of this strategy.

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

 

Figure 1: Cellular uptake of liposomes.

Figure 1: Cellular uptake of liposomes.

 

Figure 2: STR-response. Difference in STR between healthy and treated eye of mice 4 weeks after induction of acute retinal ganglion cell damage.

Figure 2: STR-response. Difference in STR between healthy and treated eye of mice 4 weeks after induction of acute retinal ganglion cell damage.

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