A recently published study reveals a connection between vision decline associated with age and proteins linked to Alzheimer’s disease. The findings might lead to novel therapies for individuals with failing eyesight from age-related macular degeneration. Researchers think that by conducting this study, they will be able to decrease the use of animals in future blindness studies.
Amyloid beta proteins are the main cause of Alzheimer’s disease, but they also start to build up in the retina as people age. The retinas of donor eyes from individuals with age-related macular degeneration (AMD) were found to possess significant amounts of AB proteins. AMD is the most prevalent cause of blindness in adults in the US.
This current research relies on prior studies that found amyloid beta accumulates around the retinal pigment epithelium (RPE), a particular cell layer located just outside of the photoreceptive layer. This layer nourishes and protects the tissue of the retina. It is also the origin of age-related macular degeneration.
To investigate this, RPE cells from normal mouse eyes and RPE cells in vitro were treated with AB by the study team. Using non-invasive diagnostic tools utilized in ophthalmology facilities, the team was able to examine the effect of the protein on real tissues of the eye using the mouse model. The researchers discovered that the mice eyes acquired retinal disease that was very comparable to that seen in humans with AMD.
“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 AB without using transgenic animals, which are often used by researchers in the field. Transgenic or genetically engineered mice can take up to a year and typically longer before AB causes pathology in the retina, which we can achieve within two weeks. This reduces the need to develop more transgenic models and improves animal welfare,” says Dr. Arjuna Ratnayaka, lead researcher and a Lecturer in Vision Sciences at the University of Southampton.
To demonstrate that hazardous amyloid beta proteins entered RPE cells and quickly accumulated in lysosomes, the cell’s waste disposal mechanism, the researchers also utilized cell models, which minimized the usage of mice in these studies. The cells did their regular job of boosting enzymes inside the lysosomes to break down this undesirable cargo.
However, the scientists discovered that around 85% of amyloid beta proteins remained inside the lysosomes, implying that the poisonous compounds would continue to build up inside RPE cells over time. Moreover, after lysosomes were overrun by amyloid beta protein, the number of lysosomes able to carry out their normal degrading job, dropped by 20%.
“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 AB which is known to drive major neurological conditions such as Alzheimer’s disease can also cause significant damage to cells in the retina,” added Dr. Ratnayaka.
The researchers anticipate that anti-AB medicines, which were previously tested in Alzheimer’s patients, will be adapted and tested as a viable therapy for age-related macular degeneration. This seems to be an area that could be investigated fairly rapidly, as many of these drugs have already been approved by regulators in the United States and the European Union.
The work may also contribute to broader attempts to avoid using animals in experiments as much as possible so that some parts of evaluating novel therapeutic therapies can go straight from model systems to patients.
“This is an impactful study that demonstrates the scientific, practical and 3Rs benefits to studying AMD-like retinal pathology in vitro,” said Dr. Katie Bates, Head of Research Funding at the National Centre for the Replacement Refinement & Reduction of animals in research (NC3Rs), which funded the research.
This study is published in Cells.