Neuroprotective Effects of Intravitreal Mesenchymal Stem Cell Transplantation in Experimental Glaucoma

被引:247
作者
Johnson, Thomas V. [1 ,2 ]
Bull, Natalie D. [1 ]
Hunt, David P. [1 ]
Marina, Nephtali [1 ]
Tomarev, Stanislav I. [2 ]
Martin, Keith R. [1 ]
机构
[1] Univ Cambridge, Ctr Brain Repair, Cambridge CB2 0PY, England
[2] NEI, Mol Mech Glaucoma Sect, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
RETINAL GANGLION-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; RETROGRADE AXONAL-TRANSPORT; HUMAN NEURAL PROGENITORS; A-INDUCED AUTOIMMUNITY; SPINAL-CORD-INJURY; RAT MODEL; STROMAL CELLS; OPTIC-NERVE; NEUROTROPHIC FACTOR;
D O I
10.1167/iovs.09-4509
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
PURPOSE. Retrograde neurotrophic factor transport blockade has been implicated in the pathophysiology of glaucoma. Stem cell transplantation appears to ameliorate some neurodegenerative conditions in the brain and spinal cord, in part by neurotrophic factor secretion. The present study was conducted to determine whether local or systemic bone marrow-derived mesenchymal stem cell (MSC) transplantation can confer neuroprotection in a rat model of laser-induced ocular hypertensive glaucoma. METHODS. MSCs were isolated from the bone marrow of adult wild-type and transgenic rats that ubiquitously express green fluorescent protein. MSCs were transplanted intravitreally 1 week before, or intravenously on the day of, ocular hypertension induction by laser photocoagulation of the trabecular meshwork. Ocular MSC localization and integration were determined by immunohistochemistry. Optic nerve damage was quantified by counting axons within optic nerve cross-sections 4 weeks after laser treatment. RESULTS. After intravitreal transplantation, MSCs survived for at least 5 weeks. Cells were found mainly in the vitreous cavity, though a small proportion of discrete cells migrated into the host retina. Intravitreal MSC transplantation resulted in a statistically significant increase in overall RGC axon survival and a significant decrease in the rate of RGC axon loss normalized to cumulative intraocular pressure exposure. After intravenous transplantation, MSCs did not migrate to the injured eye. Intravenous transplantation had no effect on optic nerve damage. CONCLUSIONS. Local, but not systemic, transplantation of MSCs was neuroprotective in a rat glaucoma model. Autologous intravitreal transplantation of MSCs should be investigated further as a potential neuroprotective therapy for glaucoma. (Invest Ophthalmol Vis Sci. 2010; 51: 2051-2059) DOI:10.1167/iovs.09-4509
引用
收藏
页码:2051 / 2059
页数:9
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