Targeting Schlemm’s Canal in the Medical Therapy of Glaucoma: Current and Future Considerations

Abstract

Schlemm’s canal (SC) is a unique, complex vascular structure responsible for maintaining fluid homeostasis within the anterior segment of the eye by draining the excess of aqueous humour. In glaucoma, a heterogeneous group of eye disorders afflicting approximately 60 million individuals worldwide, the normal outflow of aqueous humour into SC is progressively hindered, leading to a gradual increase in outflow resistance, which gradually results in elevated intraocular pressure (IOP). By and large available antiglaucoma therapies do not target the site of the pathology (SC), but rather aim to decrease IOP by other mechanisms, either reducing aqueous production or by diverting aqueous flow through the unconventional outflow system. The present review first outlines our current understanding on the functional anatomy of SC. It then summarizes existing research on SC cell properties; first in the context of their role in glaucoma development/progression and then as a target of novel and emerging antiglaucoma therapies. Evidence from ongoing research efforts to develop effective antiglaucoma therapies targeting SC suggests that this could become a promising site of future therapeutic interventions.

Childhood Lensectomy Is Associated with Static and Dynamic Reduction in Schlemm Canal Size

“…Prostaglandin analogs increase SC size, 29 but in clinical practice are considered to be less effective in aphakic or pseudophakic children than in adults. 30 New drugs that directly target extracellular matrix turnover and cell stiffness, such as adenosine A1 receptor agonists, nitric oxide donors, rho kinase inhibitors, and actin depolymerizers, are becoming available and may target SC directly 31 ; their role in pseudophakic or aphakic glaucoma is not clear. With regard to surgical treatments, AS OCT demonstrates an increase in SC size after canaloplasty in adults, correlating with a reduction in IOP.…”

Modulation of Schlemm's canal endothelial cell stiffness via latrunculin loaded block copolymer micelles

“…The first treatment group was SC cells with plain culture media; the second was SC cells incubated with unloaded micelles; the third was the SC cells incubated with 0.5 μ M Lat A solution; and the fourth group was the SC cells incubated with the Lat A‐loaded micelles at a latrunculin concentration of 0.5 μ M . Lat A of 0.5 μ M was chosen based on previous studies by our own group and others . All groups were incubated with their corresponding cocktails for 2 h. Coverslips were then gently washed with PBS and fixed with 4% paraformaldehyde (Electron Microscopy Sciences, Hatfield, PA) for 10 min at room temperature.…”

Minimally Invasive Glaucoma Surgery: What Do We Know? Where Should We Go?

“…As a surgically reachable space, SC could also provide a site to improve drug delivery and introduce a regenerative treatment to this region. [74][75][76] Another topic of interest is the role of immune cells in the aqueous humor pathways of the eye. 77 Because the behavior of immune cells could be modulated by interactions with endothelial cells, SCEs are likely to have important roles in immune responses.…”