Effects of Micropulse Laser Trabeculoplasty on Intraocular Pressure and Aqueous Humor Outflow in Pigmented Rabbits

Micropulse laser trabeculoplasty (MLT) is an established treatment for primary open-angle glaucoma; however, the mechanisms underlying its IOP-lowering effect remain incompletely understood, particularly in vivo. We investigated the mechanisms of MLT in vivo, with a focus on the trabecular meshwork outflow pathway.

Pigmented rabbits received MLT at 0 to 1500 mW, and IOP was monitored for up to 7 days posttreatment. Outflow facility was assessed, and aqueous outflow was visualized using fluorescent dextran tracer imaging. Angle tissues were collected at 1 and 7 days for quantitative RT-PCR analysis of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and extracellular matrix (ECM) components. Aqueous humor samples were analyzed for MMP enzymatic activity.

At 1000 mW, IOP was significantly reduced on day 7, and at 1500 mW, it was significantly reduced on days 3 and 7. Aqueous outflow facility was significantly increased in the 1000- and 1500-mW irradiated eyes. Tracer imaging consistently demonstrated stronger signal intensity near the angle in the 1500-mW irradiated eyes. Gene expression analysis exhibited significant upregulation of MMP-1, -3, and -9 at day 1, with sustained elevation of MMP-9 at day 7 after the 1500-mW treatment. TIMP-1 was transiently elevated, whereas TIMP-2 remained unchanged. Aqueous humor MMP activity was significantly increased at 1 day after 1500-mW irradiation.

MLT induced transient MMP activation, enhanced aqueous outflow, and reduced IOP. These findings imply that MLT lowers IOP in pigmented rabbits by promoting ECM remodeling through MMP upregulation.