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Ben Mead, Zubair Ahmed, Stanislav Tomarev; Mesenchymal Stem Cell–Derived Small Extracellular Vesicles Promote Neuroprotection in a Genetic DBA/2J Mouse Model of Glaucoma. Invest. Ophthalmol. Vis. Sci. 2018;59(13):5473-5480. doi: https://doi.org/10.1167/iovs.18-25310.
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© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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.
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