A UK study has revealed a close link between proteins associated with Alzheimer’s disease and age-related sight loss, paving the way for treatments for patients with deteriorating vision.  

Amyloid beta (Aβ) proteins are the primary driver of Alzheimer’s disease but also accumulate in the retina as people get older. Donor eyes from patients who suffered from age-related macular degeneration (AMD) have been shown to contain high levels of Aβ in their retinas. 

Building on previous research showing that Aβ collects around the retinal pigment epithelium (RPE), this study set out to establish what damage these toxic proteins cause in RPE cells. To examine the effect the protein has in living eye tissue, the researchers exposed RPE cells of normal mouse eyes and in culture to Aβ. Using non-invasive imaging techniques, they found that the mouse eyes developed retinal pathology strikingly similar to AMD in humans. 

“This was an important study which also showed that mouse numbers used for experiments of this kind can be significantly reduced in the future. We were able to develop a robust model to study AMD-like retinal pathology driven by Aβ without using transgenic animals. Transgenic or genetically engineered mice can take up to a year, and typically longer, before Aβ causes pathology in the retina, which we can achieve within two weeks,” said study lead Dr Arjuna Ratnayaka from the Department of Vision Science at the University of Southampton.  

Using cell models, further reducing the use of mice in these experiments, the researchers demonstrated that the toxic Aβ proteins entered RPE cells and rapidly collected in lysosomes, the waste disposal system for the cells. While the cells performed their usual function of increasing enzymes within lysosomes to breakdown this unwanted cargo, the study found that around 85% of Aβ still remained within lysosomes, meaning that over time the toxic molecules would continue to accumulate inside RPE cells. 

Once lysosomes had been invaded by Aβ, around 20% fewer lysosomes were available to breakdown photoreceptor outer segments, a role they routinely perform as part of the daily visual cycle, said Dr Ratnayaka. “This is a further indication of how cells in the eye can deteriorate over time because of these toxic molecules collecting inside RPE cells. This could be a new pathway that no-one has explored before. Our discoveries have also strengthened the link between diseases of the eye and the brain. The eye is part of the brain and we have shown how Aβ, which is known to drive major neurological conditions such as Alzheimer’s disease, can also cause significant damage to cells in the retina.” 

A next step could be for anti-amyloid beta drugs, previously trialled in Alzheimer’s patients, to be trialled as a possible treatment for AMD, researchers suggested.  

The study was published by Cells.