Glaucoma remains a major cause of irreversible blindness. Clinical trials have identified the following risk factors for this potentially blinding disease: older age, higher eye pressure or intraocular pressure (IOP), thinner central cornea measurement, specific genetic risk factors, and low perfusion pressure of the eye. The main treatment is to lower IOP. The IOP is a complex, physiological trait that is determined by aqueous humor fluid production, aqueous humor outflow drainage, and ocular venous pressure. The three treatment modalities to lower IOP include glaucoma medications, lasers and surgery. For the medications and lasers, the mechanisms to lower IOP involve either decreasing fluid production or increasing outflow drainage. Until recently, the main glaucoma surgical interventions (i.e., trabeculectomy and glaucoma drainage implants) lowered IOP by making a fistula that bypasses the normal outflow drainage pathways. Newer glaucoma surgical options have been developed that target the drainage angle of the eye.
Canaloplasty is a newer glaucoma angle surgery option with the intended outcome of lowering IOP in patients with glaucoma. The basic steps of canaloplasty involve: (a) catheterization and circumnavigation of Schlemm’s canal, which is the “conventional” outflow pathway; (b) dilation of Schlemm’s canal with a viscoelastic substance; and (c) placement of a tension suture in Schlemm’s canal to mechanically affect the trabecular meshwork through which the intraocular fluid traverses to drain into Schlemm’s canal. Although this procedure is highly effective to lower IOP, our lack of understanding the mechanisms involved to decrease resistance to outflow is a critical barrier to predict the surgical outcome. The goals of this interdisciplinary project focus (1) to create delivery systems that target wound healing mechanisms leading surgical failure of canaloplasty; (2) to create delivery systems that target novel pathways to lower IOP in the trabecular meshwork, Schlemm’s canal and the downstream venous pathways; and (3) to test the delivery systems in an established human eye organ culture system. The knowledge gained from our studies will bring us closer to improve and to predict surgical outcomes by controlling wound healing and strong potential to develop novel glaucoma drug classes that target these outflow drainage pathways that were challenging to target until the availability of a catheter delivery system.