Neuroprotective Effects of Intravitreal Mesenchymal Stem Cell Transplantation in Experimental Glaucoma

Thomas V Johnson, Natalie D Bull, David P Hunt, Nephtali Marina, Stanislav I Tomarev, Keith R Martin

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)2051-2059
Number of pages9
JournalInvestigative Ophthalmology & Visual Science (IOVS)
Volume51
Issue number4
DOIs
Publication statusPublished - Apr 2010

Keywords

  • Animals
  • Intraocular Pressure
  • Rats, Inbred Lew
  • Rats, Transgenic
  • Retinal Ganglion Cells
  • Cell Count
  • Green Fluorescent Proteins
  • Disease Models, Animal
  • Cell Survival
  • Rats
  • Bone Marrow Cells
  • Vitreous Body
  • Rats, Sprague-Dawley
  • Mesenchymal Stromal Cells
  • Glaucoma
  • Mesenchymal Stem Cell Transplantation
  • Optic Nerve Diseases
  • Axons
  • Cell Transplantation
  • Male
  • Ocular Hypertension

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