NYSCF Collaboration Identifies Promising Drug for Treating Most Common Form of Macular Degeneration


The Context: Age-related macular degeneration (AMD) is a disease which affects 8 million Americans and can lead to severe vision loss due to death of retinal pigmented epithelial (RPE) cells in the eye. Despite its widespread impact, there are still no disease-modifying therapies for patients with dry macular degeneration, a form of the disease affecting 90% of patients. 

The Findings: By testing over 5,000 drugs in human eye cells, a team of researchers including NYSCF scientists identified a compound which could protect RPE cells from disease-related stressors.

The Importance: This study demonstrates the power of large-scale drug testing in human cells for identifying treatments that could help reverse the most common form of macular degeneration.

Imagine sitting down to have a conversation with a friend, but you cannot see their face. The world around them might be clear, but looking straight ahead of you, all you can see is a dark spot. This is a reality for millions of Americans suffering from age-related macular degeneration (AMD), a disease of the eye for which symptoms include a loss of central vision.

Wet vs. Dry Macular Degeneration

In AMD patients, the eye’s retinal pigmented epithelial (RPE) cells begin to die. When these cells are destroyed by leaking blood vessels behind the retina, we call this “wet AMD.” When the cells atrophy without damage from blood vessels, we call this “dry AMD.” Dry AMD affects roughly 90% of AMD patients, yet there are no disease-modifying therapies available to treat it.

In dry AMD, a contributor to cell death is believed to be oxidative stress, a naturally occurring stressor during the aging process resulting from energy metabolism that can damage cells by harming proteins and DNA.

Saving Stressed Cells

A new study in Experimental Eye Research from researchers at the Yale School of Medicine in collaboration with NYSCF Research Institute scientists from the NYSCF Global Stem Cell Array® team, including Drs. Scott Noggle and Daniel Paull used a stem cell model of dry AMD and to identify a drug which may help rescue RPE cells from oxidative damage. The researchers are hopeful that these protective effects could help to keep these cells alive for longer, preserving patients’ vision.

The researchers first used advanced automation techniques to test over 5,000 FDA-approved drugs on human RPE cells exposed to an environment similar to that of oxidative stress. The team found that twelve of these drugs helped protect the cells from the effects of the stressors, and one drug (ciclopirox olamine) proved to be especially well-positioned for preventing damage.

To further examine the efficacy of ciclopirox olamine, the researchers then tested it in RPE cells taken directly from patients with dry AMD as well as RPE cells derived from the stem cells of patients with the disease (made using the Global Stem Cell Array®). In both of these models, ciclopirox olamine was able to suppress effects of oxidative stress, suggesting that it may act as a successful therapeutic in patients.

Why it Matters

This study demonstrates the power of large-scale drug testing in human cells for identifying new therapies that can treat or prevent AMD. By examining thousands of already approved compounds in the actual cells affected by the disease, this process holds promise for bringing effective treatments to patients at an accelerated pace.

Journal Citation

High-throughput screening identifies compounds that protect RPE cells from physiological stressors present in AMD.

Cai H, Gong J, Abriola L, Hoyer D, Stem Cell Array Team NG, Noggle S, Paull D, Del Priore LV, Fields MA. Experimental Eye Research. 2019 Apr 10. doi: 10.1016/j.exer.2019.04.009.

Diseases & Conditions:

Macular Degeneration