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Renaud Manuguerra, Denis-Claude Roy, Mark Lesk; Cellular Therapy For Open Angle Glaucoma: Mechanism Of Tissue Regeneration By Mesenchymal Stem Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3635.
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Elevated intraocular pressure (IOP) in open angle glaucoma is often related to a dysfunction of the trabecular meshwork (TM) of the anterior chamber angle. A large number of studies involving multipotent meshenchymal stem cells (MSC) have demonstrated their ability to induce regeneration of damaged tissues and organs. The purpose of this project is to evaluate the ability of MSCs to induce regeneration of the trabecular meshwork and to assess their ability to lower IOP in open angle glaucoma.
MSC obtained from B6 mouse bone marrow were co-cultured with rat TM cells to study their differentiation potential. MSC (1X106 cells) were also injected into the anterior chamber of rat eyes harbouring experimental glaucoma caused by laser photocoagulation to the TM. Control rats received a similar injection of mouse T lymphocytes (1X106 cells) or no injection at all. The homing and repair potential of these cells and their ability to restore baseline IOP was assessed using immunohistochemistry and tonometry over 6 weeks.
After 7 days in vitro, MSC were not found to upregulate TM cell markers, such as Aquaporin-1, Pax-6, Laminin and Fibronectin. In vivo, MSC were found scattered throughout the anterior chamber angle, but migrated in significantly higher numbers towards the area of laser damage (N=15). The MSC remained in the eye for only 4 days as detected by immunofluorescence. Interestingly, the IOP of rats who received an MSC graft (1X106 cells) in the anterior chamber began to decrease significantly on day 4 when compared to the control rats (p<0.01) in a blinded study. This drop in IOP continued until ocular pressure was restored to baseline at the end of the first week in the MSC treated group (p<0.001). Baseline IOP was attained only at day 30 in the control groups. Additionally, the anterior chamber histology was restored to normal after 1 month in the MSC treated group, while demonstrating clear signs of scarring in the control groups at the same time period.
The impressive regenerative effects of MSC, along with their apparent lack of differentiation and their rapid clearance out of the anterior chamber implies a mechanism of action linked to secreted factors. This could represent a novel and promising approach in the management of open angle glaucoma
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