There are many factors that can impact our eyesight, but one common source of vision loss centers on a blockage in the major vein in the eyeball, which prevents it from draining properly and damages the retina. This is known as retinal vein occlusion, and scientists at Columbia University have developed a potential new treatment in the form of eye drops that intervene in this process to preserve retinal function, with tests on human subjects now in the works.
Retinal vein occlusion affects millions of adults around the world each year. The blockage is often the result of blood clots that cause blood and other fluids to leak into the retina, where they damage the photoreceptor cells that are crucial for sensing and responding to light. Current approaches to treatment include multiple drug injections directly into the eye, which is not only uncomfortable but also fails to prevent the loss of vision in many cases.
Given the prevalence of the condition and the limited nature of today’s treatments, there is considerable interest in developing new therapies. The Columbia University team has been working on potential solutions in mice, and recently made a very useful discovery that centers on the role of an enzyme called caspase-9.
This enzyme plays an important role in programmed cell death, a process whereby damaged or otherwise unnecessary cells are marked for destruction, so they can be cleared from the body for fresh, healthy cells to take their place. Through their experiments in mice, however, the researchers found that when retinal vein occlusion takes hold and damages blood vessels, the activity of caspase-9 spirals out of control and in turn injures the retina.
So the team experimented with a new type of therapy, in which a highly selective caspase-9 inhibitor was worked into eye drops that were administered to the mice. This topical treatment had the effect of dampening caspase-9 activity and protecting the function of the retina, by reducing swelling, boosting blood flow and preventing damage to the all-important photoreceptor cells.
“We believe these eye drops may offer several advantages over existing therapies,” says Columbia University’s Carol M. Troy, who led the research. “Patients could administer the drug themselves and wouldn’t have to get a series of injections. Also, our eye drops target a different pathway of retinal injury and thus may help patients who do not respond to the current therapy.”
Buoyed by these promising results in mice, the team has now set its sights on human subjects with preparations underway for phase 1 clinical trials. It is also hopeful that targeting caspase-9 in this way could bring about new treatments for other conditions caused by its over-stimulation, which include stroke and diabetic macular edema, another cause of blindness.
“Vascular dysfunction is at the heart of many chronic neurological and retinal disorders, because high energy demands in the brain and eye render these tissues exceptionally vulnerable to disruption in blood supply,” says the study’s first author, Maria Avrutsky,
The research was published in the journal Nature Communications.
Source: Columbia University
