Campus Units
Genetics, Development and Cell Biology, Veterinary Clinical Sciences, Biochemistry, Biophysics and Molecular Biology, Neuroscience
Document Type
Article
Publication Version
Published Version
Publication Date
6-2011
Journal or Book Title
Investigative Ophthalmology & Visual Science
Volume
52
Issue
7
First Page
4506
Last Page
4515
DOI
10.1167/iovs.11-7346
Abstract
Purpose.: To evaluate the ability of mesenchymal stem cells (MSCs) engineered to produce and secrete brain-derived neurotrophic factor (BDNF) to protect retinal function and structure after intravitreal transplantation in a rat model of chronic ocular hypertension (COH).
Methods.: COH was induced by laser cauterization of trabecular meshwork and episcleral veins in rat eyes. COH eyes received an intravitreal transplant of MSCs engineered to express BDNF and green fluorescent protein (BDNF-MSCs) or just GFP (GFP-MSCs). Computerized pupillometry and electroretinography (ERG) were performed to assess optic nerve and retinal function. Quantification of optic nerve damage was performed by counting retinal ganglion cells (RGCs) and evaluating optic nerve cross-sections.
Results.: After transplantation into COH eyes, BDNF-MSCs preserved significantly more retina and optic nerve function than GFP-MSC–treated eyes when pupil light reflex (PLR) and ERG function were evaluated. PLR analysis showed significantly better function (P = 0.03) in BDNF-MSC–treated eyes (operated/control ratio = 63.00% ± 11.39%) than GFP-MSC–treated eyes (operated/control ratio = 31.81% ± 9.63%) at 42 days after surgery. The BDNF-MSC–transplanted eyes also displayed a greater level of RGC preservation than eyes that received the GFP-MSCs only (RGC cell counts: BDNF-MSC–treated COH eyes, 112.2 ± 19.39 cells/section; GFP-MSC–treated COH eyes, 52.21 ± 11.54 cells/section; P = 0.01).
Conclusions.: The authors have demonstrated that lentiviral-transduced BDNF-producing MSCs can survive in eyes with chronic hypertension and can provide retina and optic nerve functional and structural protection. Transplantation of BDNF-producing stem cells may be a viable treatment strategy for glaucoma.
Rights
Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted.
Language
en
File Format
application/pdf
Recommended Citation
Harper, Matthew M.; Grozdanic, Sinisa D.; Blits, Bas; Kuehn, Markus H.; Zamzow, Daniel; Buss, Janice E.; Kardon, Randy H.; and Sakaguchi, Donald S., "Transplantation of BDNF-Secreting Mesenchymal Stem Cells Provides Neuroprotection in Chronically Hypertensive Rat Eyes" (2011). Genetics, Development and Cell Biology Publications. 144.
https://lib.dr.iastate.edu/gdcb_las_pubs/144
Included in
Biochemistry Commons, Cell and Developmental Biology Commons, Comparative and Laboratory Animal Medicine Commons, Molecular Biology Commons, Structural Biology Commons
Comments
This article is from Investigative Ophthalmology & Visual Science 52 (2011): 4506, doi: 10.1167/iovs.11-7346.