Simulate in the laboratory the aging of the cells responsible for age-related macular degeneration (AMD): this is what researchers at the University of Santa Barbara have achieved. They hope to be able to test different treatments to cure this common but still incurable disease.
- Researchers have recreated in the laboratory the retinal pigment epithelium, the cells implicated in AMD.
- By simulating their aging, they recreated the conditions of retinal disease.
- They hope to be able to use this innovation to develop a treatment.
Short for “age-related macular degeneration”, AMD is a disease of the retina caused by the progressive aging of the macula, the central part of the retina.
Affecting 12% of people over 60 and nearly one in four people over 75, AMD is currently the main cause of vision loss in the elderly. And it remains, to this day, incurable in its most common form, “dry AMD”.
“Part of the struggle to find a treatment option is that we haven’t been able to actually model disease progression in cell culture or in animals”explains Lindsay Bailey-Steinitz, doctoral student in the Department of Molecular, Cellular and Developmental Biology at the University of Santa Barbara (United States).
In a study published in the journal PLOS One, the researcher and her team explain that they have developed a platform on AMD. His goal is twofold: to understand cellular evolution as the disease progresses, and to develop a model that could be used to test therapies.
Degeneration reproduced in the laboratory
AMD is caused by degeneration of the macula, an area in the center of the retina where our sharpest vision is located thanks to the cones, light-sensitive cells that ensure the human eye’s visual acuity and allow it to see in color . “These are the cells that are involved in reading, face recognition, the ability to drive, etc.”details Pete Coffey, researcher at the Institute for Neuroscience Research at UCSB and co-author of the study.
Just behind the cones of the macula is a layer of retinal pigment epithelium (RPE). These cells are responsible for maintaining the health of our rods and cones, the eye’s photoreceptors. And they are the ones that stop working properly in AMD.
While there are treatments for wet AMD (when blood vessels infiltrate the retina), there is no treatment for dry AMD, which affects 9 out of 10 cases. This involves progressive degeneration of the macula simply due to the inability of EPR cells to heal.
As the EPR cells collapse in their efforts to repair themselves, a hole develops in this layer of the retina which continues to expand.
The researchers first sought to recreate this “hole” in the macula in the laboratory. They grew EPR cells on a plate with an electrode, then she removed them: this created a hole very similar to that which appears in AMD.
But, unlike real AMD, the EPR cells – which were young cells – began to heal and repair the hole left in the retina. The researchers had to subject the cells to 10 pulses of electricity over a period of 10 days so that they were no longer able to effectively repair the damage.
The hope of a therapeutic test bed
The second step consisted in understanding how the EPR cells reacted to this stress. The researchers therefore sequenced their RNA to determine which proteins they synthesized in the damaged state. They found that some of the most important genes involved in EPR cell function were suppressed, especially if the cells had been repeatedly electrified.
The team also found changes in gene expression that matched the conditions seen in AMD. Additionally, the matrix that provides structural and biochemical support to EPR cells has also changed in ways that resemble disease pathology.
Now that she knows how to simulate EPR cell degeneration, the researchers want to move on to simulating larger holes in the macula in the lab, about 6 centimeters in diameter. They also predict a similar experience with older cells, which therefore heal less quickly. “If we can improve this device, then we will have a therapeutic test bed for AMD”, concludes Professor Coffey.
