Recycling of eye light sensors is flawed in the progressive blindness of older adults


Healthy mouse retinas (at the top) with support cells (outlined in blue) and photoreceptors (purple). In the CIB2 mutant mouse retina (bottom), photoreceptors do not digest as quickly and accumulate. Credit: Saumil Sethna

With the National Eye Institute that about 11 million older adults in the United States suffer from a disease that leads to progressive blindness, known as age-related macular degeneration, researchers at the University of Maryland School of Medicine ( UMSOM) are beginning to understand what is happening to the disease, in order to develop new therapies to treat it.

Using and mice in their new study, published June 23 a Communications on Nature, showed that the process of removing damaged old light sensors from the eye is interrupted .

Although more than 50 genes have been linked to this disease, the exact mechanism behind it is unknown. Most people have a form of the disease for which no effective treatments are known.

Earlier, the senior author of a new study, Zubair M. Ahmed, PhD, professor of urinary angiology, head and neck surgery and ophthalmology at the University of Maryland School of Medicine, found that many families with urinary hearing had genetic mutations in the CIB2 protein gene. In a paper published in 2012 a Genetics of nature, Dr. Ahmed also demonstrated that CIB2 was necessary for vision in a large human family as well as in zebrafish. Now, in this latest study, his team relied on this previous work to dissect the intricate cellular mechanisms behind retinal degeneration.

The team compared healthy mouse eyes with those of a mouse designed without the CIB2 protein. The researchers observed that the CIB2 they weren’t getting rid of their old light-sensing proteins, called photoreceptors, like healthy mouse eyes did.

Recycling of eye light sensors is flawed in the progressive blindness of older adults

Healthy mouse retina (left) and CIB2 mutant mouse retina. Yellow spots indicate undigested or incorrectly digested photoreceptors. Credit: Saumil Sethna

“Photoreceptors continue to grow in tiny columns in the eye, but over time, light damages the photoreceptors. To combat this, slowly support the eye cells by eating the damaged old photoreceptors while maintaining columns of the correct length, ”says first author Saumil Sethna, Ph.D., Instructor of Otolaryngology-Head and Neck Surgery at the University of Maryland School of Medicine. “If the photoreceptors are not removed or if the process is backed up due to the slow digestion of the support cells, as in CIB2 mutant mice, the undigested material accumulates with the passage of the time, which can contribute to blindness. “

The researchers then identified several components of this photoreceptor recycling process, including a group of proteins collectively called mTORC1, that is involved in many human diseases, including cancer, obesity, and epilepsy.

Because mTORC1 plays a central decision-making role for many cellular functions, including cell waste clearance, the researchers examined mTORC1 activity in CIB2 mutant mice and found that mTORC1 was hyperactive. They confirmed that mTORC1 was also hyperactive in human eye tissue samples from people with a form of . By linking the results of mouse studies to human disease, the researchers say their findings indicate that anti-mTORC1 drugs may be effective treatments for the most common type of age-related macular degeneration. mTOR, the main component can be found in two flavors each with different functions, known as complex 1 (as mTORC1) or complex 2 (mTORC2).

“Researchers have tested many small molecules targeted at mTORC1 to treat various diseases, but the problem is that mTOR is necessary for so many other cellular functions that there are important side effects when it is played,” says Dr. Ahmed. “In our study, we found a way to regulate mTORC1 (and not mTORC2), which can overlook many of the unpleasant side effects that typically occur with mTORC1 suppression. We believe we can use our new knowledge. on this mechanism. also develop treatments for age-related macular degeneration and other diseases “.

The authors have filed a patent application to develop new therapies using the role of CIB2 in the control of mTOR (PCT / US2019 / 044745).

“Finding out the cellular mechanism behind age-related macular degeneration is the first step in being able to develop new treatments,” says E. Albert Reece, MD, Ph.D., MBA, executive vice president for medical affairs, UM Baltimore, and the distinguished professor and dean John Z. and Akiko K. Bowers of the University of Maryland School of Medicine. “Using the evolving understanding of the mechanistic role of mTORC1, this study has provided great insights into new ways in which researchers can begin to find ways to preserve, treat, and / or improve the macular system. , and thus improve the quality of life and independent living of many . ”

New mechanism identified behind blindness in older adults

Citation: Recycling of Eye Light Sensors is Defective in Progressive Blindness in Older Adults (2021, June 23) Retrieved June 23, 2021 at recycling-eye-sensors-faulty-older. html

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