Mechanism that Causes Cataracts Discovered in Mice: The Latest in Nutrition and Vision at the HNRCA

by Nusheen Orandi

Although it may be hard to see through seven feet of snow and gray slush, the Human Nutrition Research Center on Aging (HNRCA) is still hard at work, especially in the Nutrition and Vision lab.

The Nutrition and Vision lab, directed by Dr. Allen Taylor, just published a paper in the Janurary Online Early Edition of Proceedings of the National Academy of Sciences about how tinkering with one protein, called ubiquitin, leads to other biochemical reactions that result in the clouding of the eye lens, known as cataracts. Not only is this publication groundbreaking in vision academia, but this knowledge applies to other diseases in the body that are affected by the same process, such as Alzheimer’s and Parkinson’s disease. Dr. Taylor is a Professor of Nutrition at Tufts University Friedman School of Nutrition Science and Policy, Professor of Ophthalmology at the School of Medicine, and part of the faculty of the Department of Developmental, Molecular, and Chemical Biology at the Sackler School of Graduate Biomedical Sciences. He gave insight to the progress of the lab, where nutrition fits in, and where research is going from here.

How does it work?

Many age-related diseases, like cataracts, are related to the accumulation of damaged or abnormal proteins. Ubiquitin is a protein part of a proteolytic (protein breakdown) pathway that regulates this protein buildup to prevent a number of diseases. As Dr. Taylor put it, ubiquitin is important for “cleaning up bad proteins.”

“We’re interested in what forms cataracts and age-related macular degeneration and its nutritional correlate,” he explained. Dr. Taylor and his colleagues examined how damage to the ubiquitin proteolytic pathway can cause the improper degradation of these bad proteins to lead to cataract formation.

In the experiment, Dr. Taylor and his research team identified a mechanism that leads to the formation of cataracts in the mice. The team mutated one of the lysine amino acids of the ubiquitin protein, which altered gap junction proteins called connexins and caused calcium to be retained in the cells of the eye lens. The resulting levels of calcium initiated the biochemical pathway of another protein called calpain, which is a digestive enzyme responsible for shredding proteins. The hyperactivation of calpain in the eye eventually led to the opaqueness of the lens, known as a cataract.

Cataracts are the leading cause of blindness worldwide and affect over 85% of the elderly. The inefficient degradation of proteins that cause cataracts is a significant investigation. The same ineffective ubiquitin proteolytic pathway leads to congenital cataracts as well, which is the leading cause of childhood blindness.

So, what does nutrition have to do with it?

Diet affects many diseases, and cataracts are no exception. Although having cataracts is mainly an age-related disease, nutrition can impact disease development.

“There’s a nutritional correlate to inefficient proteolysis,” Dr. Taylor explained. “It can be caused by anything that causes too much stress in the body. If you have inefficient nutrition, you won’t have enough antioxidants, and this causes oxidative stress. It messes up the proteolytic pathway and disease builds up. You don’t have enough proteolytic machinery to fight these toxic proteins.” An example he gave was having a diet high in sugar and lacking fruits and vegetables. The excess sugar causes oxidative stress on the body that accumulates with age. Without the proper antioxidants, regulatory proteins like ubiquitin can’t operate at maximum capacity. Eat healthfully because it affects your vision!

Is this research only related to vision?

No, and that’s what makes this research even more exciting. The accumulation of toxic proteins and ineffective proteolysis mechanisms is also related to neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease. Maybe you thought ubiquitin was a curious name for a regulatory protein, but it was actually a conscious term, being ubiquitous, or everywhere, in the body.

“Protein buildup takes place everywhere, like the brain,” offered Dr. Taylor. This relates to Alzheimer’s disease, where without the proper proteolysis mechanisms, plaques can form and cause the gradual neuronal breakdown. Defective ubiquitin proteosome in the brain, caused by oxidative stress and inflammation by the neurotoxin known as MPTP, is associated with one of the causes of Parkinson’s disease.

The Nutrition and Vision Lab at the HNRCA demonstrated the importance of adequate nutrition on age-related diseases, such as cataract formation, giving further indications of a parallel with Alzheimer’s disease and Parkinson’s disease. How we take care of ourselves goes a long way and causes a domino effect of all the biochemical pathways in our body.

Nusheen Orandi is a first-year student from California in the Nutrition Communication program and likes to spend her time tea-shop hunting, tensely watching the Tottenham Hotspurs, and cooking and eating with friends and family.

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