Exosomes: The New Frontier in Early Detection of Macular Degeneration

Reviewed by Preeti Subramanian, PhD, BrightFocus Foundation 

One of the earliest signs of age-related macular degeneration (AMD) is the emergence of drusen, which are tiny deposits under the retina that often contain proteins and fats. Drusen rarely cause symptoms, but they do signal the onset of dry AMD—an early form of the disease that indicates a high risk for vision loss in the future. 

How does drusen form in the first place, and how does that process lead to the progression of AMD? The answers may lie in fluid-filled sacs in the eye known as exosomes, which carry cellular products such as proteins. BrightFocus Foundation Macular Degeneration Research-funded scientist Miguel Flores-Bellver, PhD, is studying the cellular components of exosomes in a quest to define how they contribute to drusen formation. He is an assistant professor of ophthalmology at the University of Colorado School of Medicine and a principal investigator at the CellSight - Ocular Stem Cell and Regeneration Program.  

Dr. Flores-Bellver’s ultimate goal is to identify specific molecules in exosomes that could serve as biomarkers for AMD. Those biomarkers could help identify people who face a high risk of vision loss from AMD, potentially guiding early treatments and improving outcomes. 

“For those at risk of blindness, timing is everything with this disease,” Dr. Flores-Bellver said. “If we can diagnose AMD early, even before the presence of drusen, we would be able to apply therapies that may preserve vision.” 

A Passion for Eye Health

For Dr. Flores-Bellver, improving eye health is a personal passion. When he was finishing college, he was diagnosed with keratoconus in both eyes, a disease that causes the cornea to become misshapen and disrupts vision. “I decided to gain further experience in research, and during my master’s studies, I was fortunate to be introduced to the biology of the eye,” Dr. Flores-Bellver said. As he built his technical and surgical skills, he became interested in researching retinal diseases.  

Then his father was diagnosed with dry AMD. Now, he said, “I can better understand the uncertainty of having dry AMD without knowing where or when [the disease] would be progressing.”  

Dr. Flores-Bellver’s research is focused on how exosomes are affected by autophagy, a natural process critical to maintaining cell health where cells break down and recycle damaged parts. He has set out to understand how autophagy and exosome pathways in retinal pigment epithelium (RPE) and retinal cells contribute to drusen formation and AMD progression. With that understanding, he hopes to identify potential biomarkers for AMD.  

In 2021, Dr. Flores-Bellver’s team published research suggesting that as RPE cells age, they may release more proteins through exosomes, and that process could contribute to drusen formation. That led him to suspect that exosome release compensates for impaired autophagy in AMD, but that this system may break down over time.  

“The lack of therapies to prevent or reverse AMD is due to our limited understanding of the mechanisms associated with drusen formation. Our research will clarify how changes in autophagy affect what gets packaged into exosomes and determine how [exosomes] contribute to drusen formation,” he said. 

Improving Early Diagnosis of Age-Related Macular Degeneration 

The next step for Dr. Flores-Bellver and his team is to identify molecules released in exosomes and define their role in drusen formation. Using donated human samples of AMD-affected eye tissues, they will apply advanced technologies to track the release of exosomes from RPE cells and look at differences in exosome cargo in AMD. Because exosomes can travel through the body via fluids such as tears and blood, Dr. Flores-Bellver plans to study whether they could be used as biomarkers for diagnostics to detect AMD early and monitor its progression over time. 

"I truly thank the BrightFocus family, the scientific committee, and Dr. Hollyfield for this incredible recognition as an early-career investigator."

Dr. Flores-Bellver was recently honored with BrightFocus Foundation’s Dr. Joe G. Hollyfield New Investigator Award for Macular Degeneration Research. This annual award recognizes scientists who have particularly innovative approaches to research aimed at preventing and treating macular degeneration. “I was thrilled to receive this award, and I know I couldn't have achieved this without the support of my department and my mentors, including Drs. Jim Handa (JHU), Debasish Sinha (JHU), Joe Brzezinski (CU), and Val Canto-Soler (CU),” he shared. 

“This study will contribute to our understanding of how drusen is formed and identify potential biomarkers,” said Preeti Subramanian, PhD, Director of Vision Science Programs at BrightFocus. “It will aid in developing effective treatments and early diagnostic tools, significantly impacting the management of dry AMD.”  

Today, ophthalmologists monitor patients with dry AMD to track changes in the retina and recommend dietary supplements and other lifestyle changes to try to slow the disease’s progression. Dr. Flores-Bellver knows from his own family’s experience that much more is needed. “I am in my early 40s, with a predisposition and a high chance of developing AMD,” he said. “I now have a lot of great reasons to be motivated, study drusen development, and try to address some of the unknown AMD questions.”

Additional Resources:   

• Dry vs. Wet Age-Related Macular Degeneration: What’s the Difference? 
• What Causes Macular Drusen? 
• What is the Difference Between Hard and Soft Drusen? 

About BrightFocus Foundation          

BrightFocus Foundation is a premier global nonprofit funder of research to defeat Alzheimer’s, macular degeneration, and glaucoma. Through its flagship research programs — Alzheimer’s Disease Research, National Glaucoma Research, and Macular Degeneration Research — the Foundation has awarded nearly $300 million in groundbreaking research funding over the past 51 years and shares the latest research findings, expert information, and resources to empower the millions impacted by these devastating diseases. Learn more at brightfocus.org.    

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