An Ex Vivo Model of Oxidative Stress Induced Trabecular Meshwork Dysfunction for Glaucomca Research

Abstract

Affecting more than 70 million people worldwide, glaucoma is one of the leading causes of vision loss and blindness. Although the exact origins of glaucoma are still unknown, elevated intraocular pressure is a well-established risk factor. Intraocular pressure is primarily regulated by the trabecular meshwork, a tissue located in the anterior segment of the eye which drains aqueous humor. The cellularity of the trabecular meshwork is shown to be significantly reduced in glaucoma. This loss of cellularity presumably leads to reduced trabecular meshwork function and increased outflow resistance, which in turn leads to elevated intraocular pressure. In order to assess regenerative medicine therapies for glaucoma, the damage to the trabecular meshwork observed in glaucoma must be properly modeled. This study demonstrates that oxidative stress caused by hydrogen peroxide can reduce trabecular meshwork cellularity to glaucomatous levels in a porcine anterior chamber organ culture model. The diminished trabecular meshwork cellularity resulted in a loss of intraocular pressure homeostasis and the hydrogen peroxide treatment did not permanently damage the trabecular meshwork. This porcine organ culture model provides a platform for evaluating trabecular meshwork regenerative medicine therapies that could be possibly used to treat glaucoma.