Mesenchymal stem cell-derived small extracellular vescicles promote neuroprotection in a genetic DBA/2J mouse model of glaucoma

Ben Mead, Zubair Ahmed, Stanislav Tomarev

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24 Citations (Scopus)
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Abstract

PURPOSE: To determine if bone marrow-derived stem cell (BMSC) small extracellular vesicles (sEV) promote retinal ganglion cell (RGC) neuroprotection in the genetic DBA/2J mouse model of glaucoma for 12 months.

METHODS: BMSC sEV and control fibroblast-derived sEV were intravitreally injected into 3-month-old DBA/2J mice once a month for 9 months. IOP and positive scotopic threshold responses were measured from 3 months: IOP was measured monthly and positive scotopic threshold responses were measured every 3 months. RGC neuroprotection was determined in wholemounts stained with RNA binding protein with multiple splicing (RBPMS), whereas axonal damage was assessed using paraphenylenediamine staining.

RESULTS: As expected, DBA/2J mice developed chronic ocular hypertension beginning at 6 months. The delivery of BMSC sEV, but not fibroblast sEV, provided significant neuroprotective effects for RBPMS+ RGC while significantly reducing the number of degenerating axons seen in the optic nerve. BMSC sEV significantly preserved RGC function in 6-month-old mice, but provided no benefit at 9 and 12 months.

CONCLUSIONS: BMSC sEV are an effective neuroprotective treatment in a chronic model of ocular hypertension for 1 year, preserving RGC numbers and protecting against axonal degeneration.
Original languageEnglish
Pages (from-to)5473-5480
Number of pages8
JournalInvestigative Ophthalmology & Visual Science (IOVS)
Volume59
Issue number13
DOIs
Publication statusPublished - 1 Nov 2018

Keywords

  • glaucoma
  • DBA/2J
  • mesenchymal stem cells
  • extracellular vesicles
  • exosomes
  • retinal ganglion cells

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