Abstract
Purpose: :
Glaucoma is characterized by progressive retinal ganglion cell (RGC) death and optic nerve degeneration. Retrograde neurotrophic factor transport blockade has been implicated in glaucomatous pathophysiology. Stem cell transplantation ameliorates some neurodegenerative conditions, apparently by neurotrophin secretion. This study was conducted to evaluate bone marrow-derived mesenchymal stem cell (MSC) transplantation as a novel neuroprotective glaucoma therapy.
Methods: :
MSCs were isolated from adult transgenic rats with ubiquitous green fluorescent protein expression. In vitro, organotypic retinal explants were co-cultured with or without 3x103 MSCs for one week. RGC survival was assessed by immunohistochemistry. In vivo, live or dead MSCs were syngeneically transplanted intravitreally (3x104 cells) one week before, or intravenously (5x106 cells) on the day of, intraocular pressure (IOP) elevation by trabecular meshwork laser photocoagulation. Four weeks later, ocular MSC localization and integration were determined by immunohistochemistry. Optic nerve damage was assessed by axon quantification within optic nerve cross-sections.
Results: :
In vitro,
Conclusions: :
MSCs were strongly neuroprotective when cultured with retinal tissue in vitro and when transplanted locally but not systemically in a rat glaucoma model in vivo. Autologous intravitreal MSC transplantation should be considered as a potential neuroprotective therapy for glaucoma.
Keywords: neuroprotection • optic nerve • transplantation