Unlocking Secrets of Waste Disposal in the Eye
By Lisa Catanese
Reviewed by Preeti Subramanian, PhD
Within the human eye is a busy waste management center. Bacteria, dead cells, and other microscopic waste products are continuously destroyed or repurposed. It’s one of the many jobs of the retinal pigment epithelium (RPE), a hardworking layer of cells next to the retina, which is the light-sensitive tissue at the back of the eye.
The RPE has a role in phagocytosis, a cellular function involving engulfing and clearing unnecessary particles of photoreceptor outer segments, which is essential for photoreceptor health and vision.
The RPE is also involved in another form of cellular housekeeping known as autophagy (cellular self-recycling process), a critical clearance mechanism for cell’s internal debris that helps safeguard the health of the RPE. A decline in the function of the autophagic process is implicated in the development of age-related macular degeneration (AMD).
Now, for the first time, a team including BrightFocus Macular Degeneration Research grantee Aparna Lakkaraju, PhD, has identified a molecular pathway that can play a role in the eye’s waste-clearing process (phagocytosis) even under conditions of dysfunctional autophagy.
A new mechanism of waste management
The research of Dr. Lakkaraju, who serves on the BrightFocus Macular Degeneration Research Scientific Review Committee, and her colleagues at the University of California, San Francisco, involves a protein called optineurin, which primarily functions as an autophagy receptor. A loss of optineurin function is linked to neurodegenerative diseases like glaucoma and amyotrophic lateral sclerosis (ALS).
At the start of their research, the team had faced a conundrum on how the RPE cells balance and prioritize the daily clearing process or phagocytosis even under disease states. They found that the RPE prioritizes clearance of photoreceptor outer segments in AMD.
“In other words,” according to an online post from Dr. Lakkaraju, “the RPE practices intelligent altruism!”
The team investigated how RPE balances and prioritizes debris removal. They identified that optineurin, a previously unknown player in the phagocytosis process, can tag certain particles for priority recycling in the retina. This tagging was shown to ensure outer segment degradation under conditions of impaired autophagy in macular degeneration models.
AMD can develop if the eye’s waste clearance system doesn’t work properly. This study offers valuable insights into how the selective control of clearance mechanisms might sustain the metabolic health of RPE cells which may then be leveraged to mitigate AMD.
The team’s research findings were published in the journal Current Biology.
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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 $290 million in groundbreaking research funding over the past 50 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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