April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Comparison of Visual Preservation After Transplantation of BDNF or GDNF Secreting Mesenchymal Stem Cells in Glaucomatous Rat Eyes
M. M. Harper; D. S. Sakaguchi; M. H. Kuehn; Y. H. Kwon; R. H. Kardon; A. Bemelmans; C. Kostic; Y. Arsenijevic; S. D. Grozdanic
Author Affiliations & Notes
  • M. M. Harper
    Veterinary Clinical Sciences,
    Iowa State University, Ames, Iowa
  • D. S. Sakaguchi
    Genetics, Development and Cell Biology,
    Iowa State University, Ames, Iowa
  • M. H. Kuehn
    Department of Ophthalmology, Univeristy of Iowa, Iowa City, Iowa
  • Y. H. Kwon
    Department of Ophthalmology, Univeristy of Iowa, Iowa City, Iowa
  • R. H. Kardon
    Department of Ophthalmology, Univeristy of Iowa, Iowa City, Iowa
  • A. Bemelmans
    Jules-Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland
  • C. Kostic
    Jules-Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland
  • Y. Arsenijevic
    Jules-Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland
  • S. D. Grozdanic
    Veterinary Clinical Sciences,
    Iowa State University, Ames, Iowa
  • Footnotes
    Commercial Relationships  M.M. Harper, None; D.S. Sakaguchi, None; M.H. Kuehn, None; Y.H. Kwon, None; R.H. Kardon, None; A. Bemelmans, None; C. Kostic, None; Y. Arsenijevic, None; S.D. Grozdanic, None.
  • Footnotes
    Support  Veterans Administration, Fight For Sight, Department of Defense
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 2754. doi:
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      M. M. Harper, D. S. Sakaguchi, M. H. Kuehn, Y. H. Kwon, R. H. Kardon, A. Bemelmans, C. Kostic, Y. Arsenijevic, S. D. Grozdanic; Comparison of Visual Preservation After Transplantation of BDNF or GDNF Secreting Mesenchymal Stem Cells in Glaucomatous Rat Eyes. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2754.

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Abstract

Purpose: : To functionally and morphologically characterize the retina and optic nerve after transplantation of Brain-derived neurotrophic factor (BDNF) and Glial-derived neurotrophic factor (GDNF) secreting mesenchymal stem cells (MSCs) into glaucomatous rat eyes.

Methods: : Chronic ocular hypertension (COH) was induced in Brown Norway rats. Lentiviral constructs were used to transduce rat MSCs to produce BDNF, GDNF, or green fluorescent protein (GFP). The fellow eyes served as internal controls. Two days following COH induction, eyes received intravitreal injections of transduced MSCs. Electroretinography was performed to assess retinal function. Tonometry was performed throughout the experiment to monitor IOP. 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 and GDNF from lentiviral-transduced MSCs was verified using ELISA, and a bioactivity assay. Ratio metric analysis (COH eye/ Internal control eye response) of the Max combined response A-Wave showed animals with BDNF-MSCs (23.35 ± 5.15%, p=0.021) and GDNF-MSCs (28.73 ± 3.61%, p=0.025) preserved significantly more visual function than GFP-MSC treated eyes MSCs (18.05 ± 5.51%). Animals receiving BDNF-MSCs also had significantly better B-wave (33.80 ± 7.19%) and flicker ERG responses (28.52 ± 10.43%) than GFP-MSC treated animals (14.06 ± 12.67%; 3.52 ± 0.07%, respectively). Animals receiving GDNF-MSC transplants tended to have better function than animals with GFP-MSC transplants, but were not statistically significant (p=0.057 and p=0.0639).

Conclusions: : Mesenchymal stem cells are an excellent source of cells for autologous transplantation for the treatment of neurodegenerative diseases. We have demonstrated that lentiviral- 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 specific neurotrophic factors to the retina.

Keywords: neuroprotection • transplantation • electrophysiology: non-clinical 
© 2009, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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