New eye drops can prevent a common cause of blindness

Researchers at Columbia University Irving Medical Center have developed eye drops that could prevent vision loss after retinal vein occlusion, a leading cause of blindness for millions of adults worldwide.

A study in mice suggests that experimental therapy, which targets a common cause of neurodegeneration and vascular leakage in the eye, could have broader therapeutic effects than existing medications.

The study was published in Nature’s Communications.

What is retinal vein occlusion?

Retinal vein occlusion occurs when a main vein that drains blood from the retina is blocked, usually due to a blood clot. As a result, blood and other fluids leak into the retina, damaging specialized light-sensing neurons called photoreceptors.

Standard treatment for the condition is currently based on medications that reduce fluid loss from blood vessels and abnormal growth of blood vessels. But there are significant drawbacks. These therapies require repeated injections directly into the eye, and for patients who challenge this daunting prospect, the treatment ultimately does not prevent vision loss in most cases.

The new treatment targets an enzyme called caspase-9, says Carol M. Troy, MD, Ph.D., professor of pathology, cell biology and neurology at the Taub Institute for Research on Alzheimer’s Disease and Aging. Cerebral at Columbia University Vagelos. College of Physicians and Surgeons, who led the studies. Under normal conditions, caspase-9 is believed to be primarily involved in programmed cell death, a strictly regulated mechanism to naturally kill damaged or excess cells.

However, in mouse studies, Troy’s lab found that when blood vessels are injured by occlusion of the retinal vein, caspase-9 becomes uncontrollably activated, triggering processes that can damage the retina.

Eye drops prevent retinal injury

Troy’s lab found that a highly selective caspase-9 inhibitor, administered in the form of eye drops, improved a variety of clinical measures of retinal function in a mouse model of the condition. Most importantly, the treatment reduced swelling, improved blood flow, and decreased neural damage to the retina.

“We believe that these eye drops can offer several advantages over existing therapies,” says Troy. “Patients would be able to administer the medication themselves and would not have to receive a series of injections. In addition, our eye drops target a different path of retinal injury and therefore may help patients who do not respond to current therapy. “

Next steps

Researchers are preparing to evaluate eye drops in people with retinal vein occlusion during a phase I clinical trial.

In the future, Troy’s lab will also study whether caspase-9 inhibitors can be used to treat other vascular injuries caused by enzyme overactivation, including diabetic macular edema (another common cause of blindness) and stroke.

“Vascular dysfunction is at the heart of many chronic neurological and retinal disorders, because the high energy demands on the brain and eyes make these tissues exceptionally vulnerable to disruption of the blood supply,” says the study’s first author. , Maria Avrutsky, Ph.D., postdoctoral research scientist in pathology and cell biology at the Vagelos College of Physicians and Surgeons at Columbia University.