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D. S. Sakaguchi, M. M. Harper, S. G. Grozdanic, B. Blits, M. H. Kuehn, Y. H. Kwon, R. L. Reger, D. J. Prockop, M. B. Bunge, R. H. Kardon; Preservation of Visual Function After Intraocular Transplantation of BDNF Secreting Mesenchymal Stem Cells in Glaucomatous Rat Eyes. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1303.
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To functionally and morphologically characterize the retina and optic nerve after transplantation of brain-derived neurotrophic factor (BDNF) secreting mesenchymal stem cells (MSCs) into glaucomatous rat eyes.
Chronic ocular hypertension (COH), an inducible model used for study of glaucoma, was induced in Brown Norway rats by laser cauterization of the trabecular meshwork and episcleral veins. Lentiviral constructs were used to transduce rat MSCs to produce BDNF, or as a control, green fluorescent protein (GFP) only. The fellow right eyes in all animals served as internal controls. Two days following COH induction, eyes received intravitreal injections of the lentiviral transduced MSCs. Electroretinography was performed to assess retinal function. Tonometry was performed throughout the experiment to monitor intraocular pressure in the glaucomatous and control eyes. 42 days after MSC transplantation, rats were euthanized and the eyes and optic nerves were prepared for analysis.
Increased expression and secretion of BDNF from lentiviral-transduced MSCs was verified using ELISA, and bioactivity of the BDNF was assessed using a neurite outgrowth assay from cultured embryonic rat dorsal root ganglia. Following transplantation into glaucomatous eyes, BDNF-MSCs preserved significantly more visual function than GFP-MSC treated eyes. The BDNF-MSC transplanted eyes also displayed a greater level of morphological preservation of the retina and optic nerves in comparison to those eyes that received the control, GFP-MSCs.
Mesenchymal stem cells are an excellent source of cells for autologous transplantation for the treatment of neurodegenerative diseases. We have demonstrated that lentiviral-BDNF transduced MSCs can survive following transplantation and preserve visual function in glaucomatous eyes. These results suggest that MSCs may be an ideal cellular vehicle for delivery of neurotrophic factors for neuroprotection to the damaged retina and CNS.
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