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From Eye Fluid to Gene Therapies: Insights from Ocular Research

Posted by Ilena Di Toro | Posted on April 30, 2024

We’re all getting older and despite how well we take care of ourselves, aches, pains and generally not being as spry as we used to be, make themselves known. What about our eyes? What can be done at the cellular level to keep our vision in tip-top shape and treat eye disease?

First, you need to know how the eye ages in order to find treatment targets for many eye diseases. Researchers at Stanford University have found, through their study of eye fluid, a way to measure ocular aging. This can be a pathway for treatment for various eye diseases.

The fluid was collected in patients with three kinds of eye diseases: diabetic retinopathy, retinitis pigmentosa and uveitis. Scientists studied almost 6,000 proteins in the fluid between the lens and the cornea, known as the aqueous humor. Through the use of artificial intelligence (AI), researchers developed an eye-aging clock that shows which proteins speed up aging in each disease and these proteins show promise as potential new targets for treatments.

Scientists first trained the AI algorithm using the aqueous humor from 46 healthy patients to predict the age of the patient. Next, they fed the algorithm the proteins that they found in the aqueous humor to see if some of these proteins could predict the patient’s age. As a result, they found 26 proteins that could predict a patient’s age when used as a group.

The most telling thing from this study is that some cells that are common treatment targets were found to not be the ones most involved in disease. For example, diabetes drugs target blood vessel cells because they become leaky, but researchers found an increase in proteins in macrophages, the immune cells that remove dead cells. They also found that some cells aged very quickly before symptoms appeared. So, this study suggests that treating the molecular pathway early could prevent damage from disease.

What about when the damage is already done, such as when nerves are damaged in the brain and eye? Damaged nerves do not grow back. Of course, there is research taking place at the University of Connecticut (UConn) Health that involve gene therapies.

When injuries sever large bundles of axons, what are commonly known as nerves, paralysis, blindness and other injuries can occur. The axons don’t repair themselves for various reasons, one of which is that they lose the ability to grow as the nervous system matures during and after birth. Researchers found that this happens as the result of the loss of key proteins.

There are a group of genes that are dormant in mature nerve cells that are vital for axon growth and regeneration. Scientists looked at a group of 80 ribosomal protein genes and tracked how they changed during development. They found that all 80 become less active as the nerve cells mature. The ribosomal proteins are necessary for making ribosomes, the factories in the cells that make protein. As embryonic nerve cells finish growing, the need for ribosomes goes down and the ribosomal genes become close to being inactive.

Next, scientists looked at two members of this gene family, Rpl7 and Rpl7a, which were associated with neurodegenerative diseases. They decided to alter the nerve cells so that instead of the genes being quiet, they would be expressed in the adult cells. Then scientists crushed bundles of axons from these cells to model the damage done to the optic nerve, the nerve that connects the eye to the brain. While damaged optic nerves don’t grow back and cause blindness, the neurons that have been altered to keep producing Rpl7 and Rpl7a began growing axons after the injury. These results imply that the 80 ribosomal protein genes that are found in low levels in adult nerve cells might be important for axon regeneration.

While we can’t stop getting older, scientists are learning more about what is happening in our eye at the cellular level and that, in turn, lead to treatments for various disease and eye injury. Now who wants to go for a run—to Starbucks that is.

Sources:
https://med.stanford.edu/news/all-news/2023/10/eye-aging-clock.html

https://today.uconn.edu/2023/10/youthful-proteins-help-nerves-regrow/#

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