May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Preservation of Visual Function After Intraocular Transplantation of BDNF Secreting Mesenchymal Stem Cells in Glaucomatous Rat Eyes
Author Affiliations & Notes
  • D. S. Sakaguchi
    Genetics, Devel. & Cell Biol. and Neurosci. Prog., Iowa State University, Ames, Iowa
  • M. M. Harper
    Genetics, Devel. & Cell Biol. and Neurosci. Prog., Iowa State University, Ames, Iowa
  • S. G. Grozdanic
    Vet. Clinical Sci., Coll. Vet. Med., Iowa State University, Ames, Iowa
  • B. Blits
    Netherlands Inst. Brain Research, Amsterdam, The Netherlands
  • M. H. Kuehn
    Ophthalmology and Visual Sciences, University Iowa, Iowa City, Iowa
  • Y. H. Kwon
    Ophthalmology and Visual Sciences, University Iowa, Iowa City, Iowa
  • R. L. Reger
    Center for Gene Therapy, Tulane University, New Orleans, Louisiana
  • D. J. Prockop
    Center for Gene Therapy, Tulane University, New Orleans, Louisiana
  • M. B. Bunge
    Miami Project to Cure Paralysis, Miami, Florida
  • R. H. Kardon
    Ophthalmology and Visual Sciences, University Iowa, Iowa City, Iowa
  • Footnotes
    Commercial Relationships D.S. Sakaguchi, None; M.M. Harper, None; S.G. Grozdanic, None; B. Blits, None; M.H. Kuehn, None; Y.H. Kwon, None; R.L. Reger, None; D.J. Prockop, None; M.B. Bunge, None; R.H. Kardon, None.
  • Footnotes
    Support NIGMS RO1-GM072005-01; The Glaucoma Foundation NY; VA-RRD Grant C3919R; NIH-NCRR P40RR017447
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 1303. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: 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.

Methods:: 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.

Results:: 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.

Conclusions:: 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.

Keywords: transplantation • neuroprotection • electroretinography: non-clinical 
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