Mesenchymal stem cell intracameral injection reduces intraocular pressure in a rat model of glaucoma

Abstract

Purpose: To investigate the distribution/survival and effect on intraocular pressure (IOP) of bone marrow mesenchymal stem cells (MSCs) injected in the anterior chamber of a rat model of ocular hypertension

Methods: Glaucoma model was performed by cauterization of 3 episcleral veins in Long-Evans male rat eyes to induce stable IOP increase. MSCs were isolated from rat bone marrow and characterized after plastic culture adhesion, adipocyte differentiation potential and flowcytometry assessment of CD34, CD45, CD73 and CD90. MSCs were amplified in vitro for 4 passages and tagged with quantum dot nanocrystals. Animals were divided in two groups: 1/MSCs group received 5.105cells/6µl culture Minimum Essential Medium (MEM) and 2/control group received 6µl MEM (n=10 in each). MSCs or MEM were injected into the anterior chamber of 20 days-hypertensive eyes. Following the injection, IOP was monitored twice a week for one month in a masked manner using Icare™ handle tonometer. At the end of experiment, cell distribution in the anterior segment was assessed by confocal microscopy on flat mounted corneas after counterstaining with DAPI and Alexa 488nm-phalloidin

Results: In vivo MSCs transplantation reduced IOP 3 days after the injection (from 32.8+1.4 to 26.5+1.3 mmHg [p<0.01]) during 14 days. IOPs in the MEM group did not show any significant decrease (33.1+1.1 3 days after injection, p<0.01 versus MSCs group). MSCs were mainly localized in the trabecular meshwork while some were found in the anterior peripheral part of the iris and very few on the periphery of the corneal endothelium as observed in flat mounted cornea 24 days after the injection

Conclusions: We report herein that MSC injection in the ocular anterior chamber induces a significant decrease in IOP in a rat model of ocular hypertension induced by episcleral vein cauterization. These findings corroborate the recently published results obtained in a laser-induced glaucoma model [1] futher emphasizing a significant effect of MSCs on the aqueous humor outflow. MSCs are found to preferentially home into the trabecular meshwork and not to induce significant side effects. Such preliminary results could open new avenue based on autologous cell therapy in glaucoma.

Keywords: 568 intraocular pressure • 741 transplantation • 735 trabecular meshwork