Mechanism of Action of Laser Trabeculoplasty

The overall objectives of this work are to elucidate the molecular mechanisms responsible for the  efficacy of laser trabeculoplasty and utilize this information to devise improved treatment strategies for open angle glaucoma. Glaucoma is a primary blinding disease affecting millions of people. We currently neither know what causes it, nor do we have a cure. One common treatment is laser trabeculoplasty (LTP), the application of approximately 50 very small laser burns to the trabecular meshwork (a small fluid filtering tissue at the inside interface between the cornea and sclera), which has become obstructed. This obstruction reduces the outflow of aqueous humor causing the ocular pressure to rise and cause irreversible compressive damage to the optic nerve. By some unknown mechanism, LTP reduces ocular pressure in a significant portion of glaucoma patients for ten or more years. We are attempting to understand this process. The obstruction of the aqueous outflow through the trabecular meshwork is apparently due to a build-up of extracellular matrix, the material upon which cells live. This material is normally degraded and new material replaced at a rapid rate in the trabecular meshwork; 1/2 of the material is replaced every 1.5 days. The initial degradation, which allows the turnover of this material in normal healthy eyes, is the responsibility of an enzyme called stromelysin. We have been studying this enzyme as it is affected by LTP, and find that it is dramatically increased immediately following this treatment. This increase alone is sufficient to explain the curative effects of LTP on glaucoma. In the next year, we propose to study the intermediate steps in the regulation of these stromelysin increases in response to LTP. If we could understand these intermediate steps and how they mediate the LTP response, we could devise improved protocols for this common but poorly-understood therapy for glaucoma. In addition, we have recently demonstrated that this treatment releases a “factor” into the aqueous humor, which signals the trabecular cells to respond as they do. We have been studying this factor and hope to identify it, since it could be used to enhance LTP treatment.