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Volker Enzmann, Axel Vater, Sven Klussmann, Sebastian Wolf; Effects Of Mobilized GFP-expressing Bone Marrow-derived Stem Cells In Pharmacologically Induced Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3175.
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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 a mouse model of sodium iodate (NaIO3)-induced retinal degeneration. Furthermore, to quantify retinal homing and possible rescue effects of the endogenously mobilized BMSC.
Experiments were performed in green fluorescent protein (GFP) chimeras, which received 2x106 bone marrow cells of C57BL/6 mice transgenic for GFP under the direction of the human ubiquitin C promoter after lethal irradiation (10 Gy). After two months recovery retinal degeneration was triggered by single i.v. injection of NaIO3 (25 mg/ kg). BMSC mobilization was induced by twice weekly i.v. injections of NOX-A12 (8 x 13.4 mg/kg in 5% glucose) beginning three days after NaIO3 injection. At different time points (d7, 14, 21, and 28) visual function was measured by quantifying the optokinetic reflex. Morphometric analysis of the outer nuclear layer (ONL) in H&E stained paraffin sections and immunohistochemistry for GFP and different lineage-specific markers (RPE65, GFAP; βIII tubulin) was performed at the latest time point investigated.
BMSC homed to the NaIO3-damaged subretinal space and that migration was significantly increased after NOX-A12 treatment by 273%. NOX-A12 treatment of NaCl-injected control mice did not influence the number of GFP-positive cells in the retina nor any other measured property. Functional measurement showed decreased visual acuity after NaIO3 treatment but no rescue effect following BMSC mobilization. Additionally, morphometric analysis revealed significant thinner ONL and lower number of nuclei per ONL row after NaIO3. The degeneration could not be reduced by NOX-A12-modulated BMSC migration. Furthermore, no differentiation of the migrated BMSC into retina-specific cell types could be detected by immunohistochemistry.
Treatment with NOX-A12 was able to successfully home BMSC into the damaged subretinal space. However, the migrated cells did not lead to functional or structural rescue of the retinal degeneration. Further investigations are necessary to uncover possible usefulness for retinal therapies.
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