Could Research in Key Proteins Unlock the Secrets of Age-related Cataracts?

With an estimated 95 million people worldwide affected, cataract remains the leading cause of blindness in middle-income and low-income countries.¹ In higher-income countries, age-related cataracts are one of the most common etiologies of visual impairment.² Women are statistically more likely to suffer cataracts than men (61% of women versus 39% of men).³

Cataracts affect lens transparency — without a clear lens an image can’t be sufficiently focused on the retina. Common symptoms are cloudy or hazy vision with indistinct color perception, yellow tint, poor night vision and occasionally, double vision. They can affect a patient’s ability to read, drive and operate machinery and eventually, as a degenerative condition, cause blindness.

Contributing Factors to Cataract Development

Previous studies point to oxidative damage as a contributing factor: Of the risk factors identified for cortical cataracts, those that seem most likely to cause increased oxidative damage are high sunlight exposure and diabetes.⁴ Smoking, long-term use of steroids, eye injury and (surprise, surprise) drinking too much alcohol are also said to increase the risk of developing age-related cataracts. 

To learn more about the development of age-related cataracts, the National Eye Institute has awarded a professor at the University of Arizona College of Medicine in Tucson a $1.6 million grant to investigate two protein ion channels suspected to be involved with the kind of lens cell changes that lead to cataracts.⁵

The award recipient was Dr. Nicholas Delamere, PhD, professor and head of the Department of Physiology in the College of Medicine, Tucson. He commented: “Human cataract is frequently associated with failure of the mechanisms controlled by TRPV1 and TRPV4. The hope is that studies like this might pave the way to the development of strategies to prevent or delay age-related eye diseases.”

The discovery that TRPV4 and TRPV1 interact to regulate cell function in the specialized cells of the lens was based on previous work from Dr. Delamere and his research cohort. Among their findings was that TRPV1 and TRPV4 in cells on the surface of the lens act as sensors for the control mechanisms that maintain lens structure, as well as shape, size, optical clarity, water content and focus power. Now, further research will study the molecular connection between TRPV1, TRPV4 and the cytoskeleton of the eye.

The Future of Cataract Intervention

So, what could this mean? As things stand, the only available treatment for cataracts is surgery to remove the damaged lens and replace it with an artificial one. There are some two million or so of these procedures in the United States every year alone.³ Could we potentially be looking at pre-surgical intervention for age-related cataracts? Could lens replacement surgery become a thing of the past? That’s not yet clear — and seems a bit far-fetched, at least in the short-term. Initially, the object of the study will be to gain an understanding of age-related lens cell changes and the mechanisms that underpin them. The research aims to discover the role of micro-changes in pressure on the lens surface activating TRPV1 and TRPV4 and precipitating homeostasis. 

And the stakes are high. With almost half of Americans receiving cataract treatment by the age of 75, any additional insight into the loss of lens transparency in aging adults would be welcome. If even a small percentage of surgical cataract interventions could be avoided or delayed, it would represent a significant breakthrough. 

Dr. Delamere will be assisted by an able research team comprised of Mohammad Shahidullah, DVM, PhD, research associate professor in the Department of Physiology; and Rick Mathias, PhD; and Junyun Gao, PhD, of the Department of Physiology and Biophysics at Stony Brook University. 

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