Transplantation of BDNF-Secreting Mesenchymal Stem Cells Provides Neuroprotection in Chronically Hypertensive Rat Eyes

Date
2011-06-01
Authors
Harper, Matthew
Grozdanic, Sinisa
Blits, Bas
Kuehn, Markus
Zamzow, Daniel
Sakaguchi, Donald
Buss, Janice
Kardon, Randy
Sakaguchi, Donald
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Veterinary Clinical SciencesBiochemistry, Biophysics and Molecular BiologyNeuroscienceGenetics, Development and Cell Biology
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.

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This article is from Investigative Ophthalmology & Visual Science 52 (2011): 4506, doi: 10.1167/iovs.11-7346.

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