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Carolyn Trepp, Anna Kruschinski, Axel Vater, Volker Enzmann; Rescue effects of mobilized GFP-expressing bone marrow-derived stem cells in NaIO3 induced retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5317.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate bone marrow-derived stem cell (BMSC) mobilization by NOX-A12, an SDF-1-inhibiting L-RNA aptamer (Spiegelmer), in combination with an increased SDF-1 gradient towards the sodium iodate (NaIO3)-damaged retina. Furthermore, to quantify retinal homing and possible rescue effects of the endogenously mobilized BMSCs.
Experiments were performed in GFP chimera mice which had received 2x106 bone marrow cells transgenic for GFP after lethal irradiation (10 Gy). Two months later retinal degeneration was induced by single i.v. injection of NaIO3 (25 mg/kg). On day 3 BMSC mobilization was triggered by single i.v. injection of NOX-A12 (13.4 mg/kg in 5% glucose) and intraocular injection of SDF-1 (100 ng, 200 ng or 500 ng) 4 h after NOX-A12 injection. As controls i.v. injected glucose and intraocular injection of BSS were used. The number of GFP+ cells in the retina was quantified at day 10 by immunohistochemistry (IHC). After BMSC mobilization retinal thickness was measured in HE stained sections. Homed GFP+ cells were characterized and quantified in retina sections by IHC: BMSCs (Sca-1), microglia (Iba-1) and macrophages (F4/80). Differentiation of migrated BMSCs towards retinal lineage was assessed: RPE (RPE65, bestrophin), glia (GFAP), neuronal cells (βIII-tubulin). Visual function was measured at d7, 14, 21 and 28 by quantifying the optokinetic reflex.
The highest number of GFP+ cells was found in mice treated with 500 ng SDF-1. Injection of SDF-1 increased the number of BMSCs in the retina. No further increase of SCs was seen with additional NOX-A12 treatment. Still, a trend towards less activated microglia was observed. The number of macrophages in the retina remained unaltered. No co-labelling of GFP+ BMSC with retina-specific markers was observed. No changes in retinal thickness were observed with NOX-A12, SDF-1 or combined treatment. However, a significant increase in visual acuity (P<0.05) was seen after NOX-A12+SDF-1 injection compared to NOX-A12+BSS. At d28 after NaIO3 injection visual acuity in NOX-A12+SDF-1 treated animals had significantly improved compared to only SDF-1 treated animals.
Intraocular SDF-1 injection increased migration of mobilized BMSCs into the degenerated retina. BMSCs did not differentiate to retinal cells but showed a positive effect on retinal function. The rescue effect may be mediated by soluble factors.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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