A Novel Cell-Based Therapy for Targeted Nitric Oxide Delivery to the Trabecular Meshwork for More Effective IOP Reduction in Glaucoma

Brief Lay Background

Glaucoma is a leading cause of blindness, affecting 80 million people worldwide. The only method to treat glaucoma and stop further blindness is to decrease eye pressure. Yet current glaucoma drugs often fail to achieve sufficient or sustained pressure reduction. This is partly due to patients not taking their drops, but also because current drugs do not effectively target the factors controlling eye pressure.

Pressure is determined by fluid drainage from the eye, with a blocked drain causing fluid “build up” that increases eye pressure. To effectively lower pressure, one should therefore unblock the drain, but most glaucoma drugs do not work that way.

The Overby lab has shown how a small molecule controls eye pressure by maintaining a healthy drain and preventing blockages. With ageing and glaucoma, drainage tissues become stiff, suppressing the natural healthy function of this molecule. This leads to fluid build-up and pressure elevation.

What problem/knowledge gap does it help address?

The team propose a cell-based therapy that aims to restore healthy levels of this molecule in glaucoma.

There is an unmet need for better pressure-lowering therapies to prevent vision loss in glaucoma. The ideal therapy would be safe, long-lasting, and free of unwanted side-effects. Drop-less therapies have a further advantage because they still work when patients (often elderly) forget their drops. 

Aim of the research project

To demonstrate that cell-based delivery of the molecule provides safe, long-lasting reduction of eye pressure. The team will test this idea in mice with normal or elevated eye pressure and in post-mortem human eyes. These data will provide the necessary evidence to support further development towards clinical translation.

Potential impact on people with sight loss

Blindness resulting from glaucoma is irreversible, and even in cases where eye pressure appears normal, further glaucomatous blindness is preventable by lowering eye pressure. Most glaucoma therapies, however, fail to achieve sufficient or sustained eye pressure reduction in all patients.

This cell-based therapy may benefit glaucoma patients by providing long-lasting reduction in eye pressure following a single injection without the need for further drops, thereby eliminating non-adherence issues. Further, as it is a naturally occurring molecule, there will be fewer side-effects and by delivering it directly to the drainage tissues, avoids bloodshot that is common for topical drops.