- 3 min read
Updated: Nov 22
Educational summary by Dr. Srinivasa, Medical Advisor, and team. Based on Gu S. et al., Experimental Eye Research (2024), DOI 10.1016/j.exer.2024.109862. Educational only, no product endorsement.
Age-related macular degeneration (AMD) is one of the leading causes of irreversible vision loss in older adults. In roughly 90 % of AMD cases, cells in the eye's retinal pigment epithelium (RPE) gradually deteriorate under continuous "oxidative stress". These RPE cells act as the retina’s support system, recycling waste and supplying nutrients within the eye. When they die, the central visual field progressively fades.
L-Ergothioneine (EGT) is a naturally occurring amino acid found in trace amounts in certain foods. EGT has long been recognized for its cellular antioxidant activity which can help combat RPE stress. EGT is especially interesting to scientists because unlike other natural antioxidants, it has a dedicated "transporter" protein (OCTN1) that actively carries it into RPE cells.
In this article we review a study where researchers explored EGT's potential to protect the retina itself.
Short Summary of Findings
If you just want the TL;DR on L-Ergothioneine (EGT) from the AMD study:
RPE Cell Protection: EGT dramatically increased survival of human retinal pigment cells exposed to oxidative stress — from < 20 % to ~ 94 %.
Restored Retinal Structure: In mus musculus models, EGT preserved retinal layering and prevented cell death without observable toxicity.
Cellular Repair Mechanisms: EGT preserved cell mitochondria (which power cells), and activated "NRF2", an antioxidant which helps maintain normal retinal physiology.
Together these results suggest that EGT helps retinal cells resist oxidative injury, a key driver of dry AMD progression.
RPE Cell Protection from Oxidative Stress
To model retinal damage, researchers exposed human retinal pigment epithelial (RPE) cells to an oxidative stress environment that kills over 90 % of these cells within 24 hours. When EGT was added, cell survival rose dramatically from less than 10% to nearly 95 %.
Microscopic imaging showed that EGT-treated cells retained normal shape and protective connections between neighboring cells, which are normally lost under oxidative stress. In contrast, untreated cells collapsed and disintegrated. EGT also reduced markers of cell death and DNA damage, suggesting broad protection across multiple injury pathways.
In plain language: EGT helped retinal support cells stay alive and structurally intact when under oxidative attack.
Preserving Retinal Structure and Function
The research team next tested EGT's effect on oxidative stress to the eye of a "Mus musculus" model. At an optimized dose, EGT protected the overall retinal architecture: the retinal pigment epithelium (RPE) layer remained organized, and photoreceptor cells stayed properly aligned.
Optical coherence tomography (OCT) imaging confirmed that EGT-treated eyes maintained normal retinal layering, whereas retina without an EGT dose developed severe damage. To ensure safety, the scientists also examined major organs such as the liver, heart, and kidneys, finding no evidence of toxicity.
In plain language: EGT helped keep the retina’s layers healthy and organized in a laboratory model of AMD without harmful side effects.
Retinal Cell Repair
Inside cells, oxidative stress can disrupt the delicate balance between protective and damaging molecules. By neutralizing some of this stress directly, EGT helped cells conserve and rebuild their own antioxidant reserves. For example, levels of "glutathione", the body’s primary natural defense molecule, were found to be elevated.
EGT also preserved the size and structure of cell power plant machinery (mitochondria), and stabilized cell power production (ATP levels). Both the power plants and their output are crucial for cell metabolism and vision.
The scientists dug deeper to check what was happening at a genetic level. They found that EGT activated the "NRF2 pathway". This master switch activates the cell's defense against oxidative stress. When researchers blocked NRF2 from working, EGT lost its protective effect. They had found a biological link between EGT and stable cell function during potentially damaging conditions.
In plain language: EGT seems to “reset” and reinforce the eye cell’s own defense systems, helping helping retinal support cells keep their energy levels steady and stay healthy even under oxidative pressure.
Final Thoughts
This 2024 study identifies L-Ergothioneine as a promising candidate for future AMD research. By shielding retinal support cells from oxidative damage and engaging the NRF2 repair network, EGT showed protective effects both in human-derived cell cultures and in controlled laboratory models, without evidence of toxicity.
These findings lay important groundwork for developing next-generation antioxidant approaches to support long-term retinal health.
