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

Purpose: 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. Methods: 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. Results: 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. Conclusions: 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.