Five New Foundation Research Awards Target Macular Degeneration

August 05, 2015

No other retinal condition affects more people in developed countries than the dry form of age-related macular degeneration (AMD). Of the estimated 30 million people in the world with AMD, approximately 90 percent have dry — the other 10 percent have the wet form. Yet there are no treatments for dry AMD — only a nutritional supplement, which can reduce risk of disease advancement in those with early-stage AMD by about 25 percent.

Four new awards from the Foundation Fighting Blindness support projects aimed at the root causes of dry AMD, which are based on genetics and lifestyle. Some of these efforts, however, may also advance therapy development for inherited forms of macular degeneration.

A fifth award is for development of a large-animal model for Stargardt disease, the most common form of juvenile macular degeneration.

Each grant provides up to $300,000 in research funding over three years.

“From a population standpoint, dry AMD is the largest unmet need for retinal diseases,” says Stephen Rose, Ph.D., chief research officer, Foundation Fighting Blindness. “We are excited about the potential for these new projects to make a big impact in the development of therapies to prevent vision loss from ever occurring."

Targeting the Immune System

Thanks to Foundation-funded genetic discoveries made over the last decade, researchers have found a strong link between AMD and an overly active complement system, which is part of the innate immune system. Though it normally works as a defense to ward off infection and other pathogens, the complement system can cause damage if not properly regulated.

Catherine Bowes Rickman, Ph.D., at Duke University Eye Center, received an award to explore how two proteins — CFH and FHL-1 — might be regulated in the retina to prevent complement-system activation and, ultimately, the onset of dry AMD. 

Abigail Hackam, Ph.D., at the Bascom-Palmer Eye Institute, University of Miami, also received funding to investigate the immune-system pathway for preventing vision loss from dry AMD. She has evidence that blocking the production of a protein called MyD88 may prevent damaging immune-system activity.

Targeting RPE Cells

Many forms of macular degeneration originate in a layer of cells called the retinal pigment epithelium (RPE), which provide support for photoreceptors, the cells that make vision possible. That makes these cells important therapeutic targets.

Patsy Nishina, Ph.D., at The Jackson Laboratory, received an award to investigate how mutations in the gene CTNNA1 lead to a retinal disease called Butterfly Macular Pattern Dystrophy (BPMD). This condition is characterized by RPE degeneration, following a disease pathway that’s very similar to that for dry AMD. Dr. Nishina will develope gene-corrected RPE derived from stem cells as a potential therapy for BPMD and dry AMD.

Radha Ayyagari, Ph.D., at the University of California, San Diego, will use her award to investigate a protein expressed in the RPE called CTRP5, which is implicated in a condition known as late-onset retinal degeneration, or L-ORD. She will also learn more about the protein MFRP, which binds to CTRP5 and is associated with early-onset degeneration. Dr. Ayyagari believes that investigating the roles and interaction of these two proteins can lead to a better understanding of dry AMD and a number of other retinal pathologies.

A Valuable Stargardt Disease Model for Testing Therapies

With many therapies for Stargardt disease moving toward clinical trials, a canine model of the condition will be a highly useful platform for evaluating their safety, efficacy and dosing. Large-animal models of retinal diseases are beneficial, because the eyes are similar in size to those of humans. Simon Petersen-Jones, D.V.M., Ph.D., at Michigan State University, has received funding to develop a canine model of Stargardt disease with retinal degeneration very similar to that in humans.