Macular Degeneration Risk If You Have This Gene

Researchers are continually looking at how various proteins affect the progression of illness. When it comes to eye disease, there is a specific gene that could be the root cause, holding key proteins actually coded to do serious damage to the retina. If you have this gene you could be at risk of developing macular degeneration, the leading incurable eye disease that results in blindness. However, now that this gene has been located, it may hold the key to stopping the onset of AMD (age-related macular degeneration) in some individuals. 

Chromosome 10

We all have unique chromosomes that hold coded information developed to instruct the body to perform certain functions.

A chromosome is defined as:

“a threadlike structure of nucleic acids and protein found in the nucleus of most living cells, carrying genetic information in the form of genes”.

However, sometimes chromosomes can hold gene information that may harm us due to a generational shift through decades of certain lineages. When it comes to eye health, some individuals hold what is called, “chromosome 10-directed AMD”. Chromosome 10 is fully described as “chromosome 10q26” and has long been a risk variant for macular degeneration, yet scientists could never pinpoint the exact application this chromosome adds to the degeneration of sight. 

Current work by researchers at the Sharon Eccles Steele Center for Translational Medicine (SCTM) at the University of Utah’s John A. Moran Eye Center shows the pathway of the chromosome 10 gene expression which involves a specific gene called, HtrA1. Discovering this process associated with chromosome 10 is a major breakthrough in developing a potential therapeutic pathway to slowing or even reversing the disease.

Randall J Olson, MD, Moran Eye Center CEO and Distinguished Professor of Ophthalmology and Visual Sciences commented,

“…we created the SCTM as a unique academic model designed to quickly turn discoveries into therapies through partnerships with philanthropists and industry as well as national and international scientific collaborators.”

HtrA1 

HtrA1 is produced throughout the body and works alongside other major building block processes essential for human health. Medline Plus describes this gene,

“The HTRA1 gene provides instructions for making a protein that is found in many of the body’s organs and tissues. This protein is a type of enzyme called a serine protease, which has an active center that cuts (cleaves) other proteins into smaller pieces. The HTRA1 enzyme helps break down many other kinds of proteins in the space surrounding cells (the extracellular matrix).”

The researchers at the University of Utah followed HtrA1 and how it affected the retinal pigment epithelium (RPE). This is the essential area of the eye where sight is produced and also a major location of where macular degeneration strikes. What scientists found was how this gene expression functioned, particularly when coming from chromosome 10. Up until now, researchers where unable to pinpoint the end result of HtrA1 from specific individuals, given its unique pathway that does not present in all AMD patients, therefore it was somewhat like looking for a needle in a haystack. Researchers were eventually able to find HtrA1, within chromosome 10, and follow it to the retina. This can now be associated with therapeutics to react on chromosome 10 and possibly save millions of people from going blind.

Eye Donations

The steadfast work by researchers of disease is always an astounding feat. However, before it becomes “astounding” there could be years of painstaking, slow, trial and error experimentation that only a few have the patience to follow through. Knowing for decades how chromosome 10 is a risk variant for AMD just wasn’t enough. Researchers had to find out what the mechanism was that caused the body to rob itself of sight. Although past research had shown no association, scientists at SCTM felt otherwise and began the long journey of searching for answers. 

Having no animal models available for the study of chromosome 10 had researchers scrambling for another way to look at AMD progression. Although a human trial would eventually be arranged, at this pre-research stage scientists needed a “proof of concept” to get recognition and funding for further study. This is when they came across a unique repository of donated eyes from deceased patients that had AMD and from those who did not. It was more than 8,000 pairs of eyes that lead to the breakthrough they were looking for and researchers could not be more grateful to the donation program. 

SCTM Executive Director Gregory S. Hageman, PhD commented, 

“We were able to generate these exciting results thanks to our eye donors and their families. We are so extremely grateful for their precious gifts.”

These results are a small example of the astounding progress science has made through not only eye donations but organ donations overall. 

Scientific Perseverance 

Sifting through 8,000 eyes requires a series of difficult and time-consuming experimentations, particularly when going against previous research that recorded nothing there. However, Dr. Hageman felt otherwise, stating,

“those particular studies employed too few samples and the analyses were performed using neural retina and white blood cells, rather than RPE-Bruch’s membrane, which is the primary site of AMD pathogenesis.”

As a result of these past studies, development and testing may have exacerbated AMD progression in human trials rather than slowed it down. With Dr. Hageman and his team at the University of Utah working diligently to find something, once they looked at the levels of HtrA1 on the RPE-Bruch’s membrane (a specific part of the retina often overlooked as the genesis of AMD) correlations were found. As reported by the University of Utah’s Health newsletter, 

“These variants were found to impair expression of the HTRA1 gene by the RPE, resulting in an approximately 50 percent reduction of HtrA1 protein levels at the RPE-Bruch’s membrane interface during aging. The failure to produce adequate levels of HtrA1 protein disrupts this key region of the eye and is associated with AMD-associated pathologies, including the deposition of abnormal deposits and the development of abnormal blood vessels.”

Currently, researchers are now developing a therapeutic protocol for those carrying the chromosome 10 gene to stop macular degeneration it its tracks. This is yet a small example of the capability of genomics and how scientists may soon shift from putting out fires each time they flare, to finding the fire before it starts. 

Sources:

https://medlineplus.gov/genetics/gene/htra1/

https://www.clinicalomics.com/topics/patient-care/eye-disorders/possible-treatment-pathway-for-age-related-macular-degeneration-uncovered/

https://healthcare.utah.edu/moran/news/2021/07/amd-chromosome-10-research.php