Differentiation of Bone Marrow Mesenchymal Stem Cells Into Trabecular Meshwork Cells in vivo and in vitro in Experimental Glaucoma

Abstract

Purpose: : To evaluate the ability of MSCs to differentiate into trabecular meshwork cells in vitro and in vivo, and to assess their ability to lower IOP in a rat glaucoma model.

Methods: : MSCs obtained from B6 mouse bone marrow were co-cultured with rat trabecular meshwork cells. MSCs were also injected into the anterior chamber of rat eyes harbouring experimental glaucoma caused by laser photocoagulation to the trabecular meshwork. The differentiation, homing and repair potential of these cells and their ability to restore baseline IOP was assessed using immunohistochemistry and tonometry over 6 weeks.

Results: : After 7 days in vitro, the MSC derived mouse cells were found to express trabecular cell-specific markers, such as Aquaporin-1, Pax-6, Laminin and Fibronectin. In vivo, MSCs were concentrated in the trabecular meshwork areas of rats treated with photocoagulation (N=15). The MSCs found in the damaged trabeculum expressed trabecular cell markers (aquaporine-1 and pax-6) as detected by immunofluorescence. Moreover, return to baseline IOP occurred by day 5 for rats who received MSC graft (1X10⁶ cells) in the anterior chamber. In contrast, IOP normalization occurred only by day 40 in the control rats (N=10 p<0.01). The treatment was found to be MSC dose-dependent and results were confirmed in a blinded study.

Keywords: regeneration • differentiation • trabecular meshwork