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Elad Moisseiev, Zeljka Smit-McBride, Sharon Oltjen, Pengfei Zhang, Robert J Zawadzki, Monica Motta, Christopher J Murphy, Whitney Cary, Geralyn Annett, Jan Nolta, Susanna S Park; Intravitreal Administration of Human Bone Marrow CD34+ Stem Cells in a Murine Model of Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6068. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Autologous intravitreal bone marrow CD34+ hematopoietic cells are being explored in a human clinical trial as potential therapy for retinal degeneration (registered with clinicaltrials.gov, NCT01736059). Since urine CD34+ cells are not comparable to human CD34+ cells, the purpose of this study was to examine the effect of intravitreal human CD34+ cells in a murine model of hereditary retinal degeneration, in order to further characterize the effects of these human cells on the degenerating retina.
C3H/HeJ mice, homozygous for the rd1 mutation and systemically immunosuppressed, were treated with an intravitreal injection of either PBS (n=16) or CD34+ cells (n=16) isolated from human bone marrow and labeled with EGFP. The treated eyes were imaged in vivo with simultaneous SLO/OCT retinal imaging to localize the EGFP labeled cells in the eye. ERG testing was conducted on both eyes. Animals were euthanized and the eyes were harvested for immunohistochemical and microarray analysis of the retina.
In vivo SLO fundus imaging allowed visualization of EGFP labeled cells within the eyes following intravitreal injection of CD34+. Simultaneous b-scan OCT analysis of the corresponding retina localized the EGFP labeled cells on the retinal surface. Immunohistochemical analysis of the retina identified EGFP labeled cells on the retinal surface. Phase contrast microscopy visualized the cells adjacent to the ganglion cells and the internal limiting membrane. ERG showed a flat signal both at 1 and 4 weeks following injection in both eyes in all mice. Microarray analysis of the retina showed significant alteration in expression of >300 mouse genes in CD34+ stem cell treated eyes, with predominant effects on genes in pathways regulating phototransduction, photoreceptor development and maintenance, and apoptosis.
Intravitreal injection of human CD34+ stem cells from bone marrow resulted in their intraocular survival and localization directly on top of the retina. Although the effect of this cell therapy on retinal function could not be appreciated in this murine model of rapidly progressive retinal degeneration, the molecular changes in the retina associated with human CD34+ cell therapy suggest potential paracrine trophic regenerative effects on the degenerating retina that warrant further exploration.
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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