Researchers step towards therapeutic test bed for age-related macular degeneration

As we get older, many of our body processes begin to slow down. For example, hand cuts take longer to heal after middle age than young people. However, it still heals.

Unfortunately, this does not apply to the cells behind the eyes. After the age of 65, it will not be repaired much. This allows Age-related macular degeneration (AMD), the main cause of poor vision Senior citizens.. More than 2 million cases have been reported in the United States in 2010, and the National Eye Institute estimates AMD will affect more than 3.5 million adults in the country by 2030.

Researchers at the University of California, Santa Barbara have overcome a major hurdle in creating a platform for testing treatments for this disease. The results are displayed in the journal PLOS ONE..

Our sharpest vision occurs in the center of the retina, the area called the macula. “This area is filled with cones, the cells that are needed to see the details,” said author Pete Coffey, a researcher at the Neuroscience Institute at UCSB. “They are cells involved in reading, face recognition, driving abilities, etc.”

Immediately behind it is a layer of retinal pigment epithelium (RPE) cells. These are responsible for maintaining the health of our rods and cones, the photoreceptors of our eyes. And these are the cells that don’t work properly in AMD.

There are two forms of age-related macular degeneration. Wet AMD occurs when blood vessels invade the retina. There are treatments of this kind, but they are aimed at preventing unwanted blood vessel growth.

However, about 9 out of 10 cases, including progressive degeneration of the macula due to the inability of RPE cells to heal, are called “dry AMD” by scientists. Ophthalmologists can also identify the onset of disease early, but there is currently no cure for dry AMD.

“The difficulty in finding treatment options was that we couldn’t really model disease progression in cell cultures and animals,” said Lindsay Bailey-Steinitz, a PhD student in the Department of Molecular Studies. I am. , Cells, and developmental biology.

Bailey Steinitz and her co-workers set out with two goals in mind. The first was to understand what was happening at the cellular level as the disease progressed. The other was to develop a model that could be used to test treatments.

As the RPE cells try to repair themselves, holes develop and continue to expand in this layer of the retina. Bailey Steinitz was aiming to reproduce this hole in the lab. She cultured RPE cells on plates with electrodes and then zapped them. This created a hole that was very similar to what you see in AMD.

But these were young cells, so they began to heal and repair this hole. That’s great for cells, but not for the team trying to model the disease. Therefore, Bailey Steinitz again shocked the cells. She found that after applying 10 pulses of electricity for 10 days, the cells were unable to repair the damage effectively.

To elucidate how RPE cells responded to this stress, Bailey Steinitz sequenced the RNA and identified the proteins that were synthesized in the damaged state. She found that some of the most important genes involved in RPE cell function were repressed, especially when the cells were shocked multiple times.

The team also saw changes in gene expression consistent with the conditions seen in AMD. In addition, the matrix that provides structural and biochemical support to RPE cells was altered in a manner similar to disease pathology.

“I wasn’t surprised that the RPE profile was down-regulated,” said Coffey. “If someone gives you a kick, you will feel sick.

“But I was very surprised because its immunology changed, and so did the pericellular matrix, which looked exactly like the profile seen in AMD.”

The cultured cells replicated a profile similar to a real disease, so the team is moving into a large hole about 6 mm in diameter. Bailey Steinitz is planning an experiment similar to the old one cell, Indicates a reduction in healing ability.

“If we could improve this setting, we would have a therapeutic bed for AMD,” said Coffey.