Research

Age-related macular degeneration (AMD) is caused by the deterioration of the macula, which is the area of the retina that is responsible for central vision and the ability to see color and fine detail when looking directly at an object.

About AMD

In the early stages of the most common type of AMD, tiny deposits called drusen begin to form underneath the retina. These drusen may be so insignificant that patients have few, if any, outward symptoms and rarely experience vision loss. As this form of AMD progresses, however, more disruptive drusen begin to appear. As the size and number of drusen increase, patients may notice a small dark spot in their central vision, causing them problems while reading or driving at night.

A subset of patients with early AMD will progress to the most common late form of the disease, geographic atrophy. This form of AMD is caused by the progressive death of regions of the retina, including, very often, the macula. These regions of atrophy expand over time, causing severe and irreversible vision loss. There are no therapies available to reverse or slow down the progression of geographic atrophy.

In a less common but also serious form of late AMD, abnormal blood vessels begin to develop underneath the retina. These abnormal blood vessels are unusually delicate and may bleed or leak fluid. This fluid builds up beneath the retina, causing it to bulge or lift from the back of the eye. This causes significant damage to the retina and often leads to blurred, wavy, or distorted vision. This form of AMD can progress rapidly, leading to severe vision problems in the affected eye and causing permanent vision loss.

Dr. Hageman was one of the first scientists to identify genetic mutations increasing the risk of developing AMD. Following years of genetic research, he and his team have demonstrated that AMD is at least two biologically distinct diseases.

  • The most common in the United States is caused by the dysregulation of the complement system, a key part of our immune system, and is associated with a cluster of genes on chromosome 1 (CFH-CFHR5).
  • The second most common form is driven by a breakdown of structures and elements essential to the survival of the retina with age. This breakdown is caused by a mutation in the ARMS2/HTRA1 gene on chromosome 10.

People with two copies of risk genes on chromosomes 1 and 10 almost always develop AMD and are more likely to suffer from severe vision loss at a younger age.

Because distinct biological mechanisms drive these two forms of the disease, they require different therapeutic approaches. Dr. Hageman and his team have developed therapies adapted specifically to chromosome 1- or chromosome 10-directed AMD, some of which have reached the pre-clinical stage.

Research Timeline

1987—Eye Repository

Dr. Hageman begins collecting human eye donations to examine the biology of AMD. Today, his repository includes more than 8,500 pairs, the largest in the world dedicated to studying normal and diseased retinal tissue. SCTM eye tissue staff members are on call 24 hours a day, every day, to receive and process donated human eye tissue. Microscopy photos, clinical ophthalmological data and images, medical history, and genetic data all help to provide a detailed picture of how AMD occurs, which allows researchers to develop treatments.

2000Landmark Finding

Dr. Hageman discovers that abnormalities in the Complement Factor H (CFH) gene on chromosome 1, which regulates a part of the body’s immune system, are associated with an increased risk for, or protection from, developing AMD. He files numerous patent applications and publishes his work in 2005.

2006NIH Funding

The National Institutes of Health awards Dr. Hageman $23 million to study the role of CFH in disease. The program includes colleagues from 12 national and international institutions.

2007Growing Support

Dr. Hageman founds Optherion, Inc., which raises $45 million to develop therapies for AMD.

2009New Opportunity in Salt Lake City

Drs. Hageman and Olson establish Moran’s Center for Translational Medicine (CTM) to quickly and cost-effectively turn scientific discoveries into diagnostics and therapies for blinding eye conditions, with a focus on AMD. The CTM is later renamed the Sharon Eccles Steele Center for Translational Medicine (SCTM) in honor of Sharon Eccles Steele, who pledged $9 million to support its mission as part of a larger fundraising campaign supported by many generous donors.

2010Genetic Study

The SCTM begins recruiting participants for an ongoing genetic study of AMD. More than 4,800 people, with and without AMD or a family history of the disease, are enrolled so far. Study participants are screened and genotyped for future AMD treatment trials. The effort includes a partnership with the Utah Population Database, one of the world’s richest sources of genetic and other in-depth health information.

2011Two Distinct Diseases

Dr. Hageman and his team confirm AMD is at least two distinct diseases, with a cluster of genes on chromosome 1 that affects the immune system and a gene on chromosome 10 that alters levels of protein at the back of the eye (Htra1), causing the second form of the disease.

  • The SCTM’s Burt Richards, PhD, is leading SCTM efforts to develop a protective drug to block AMD caused by chromosome 1. 
  • The SCTM’s Brandi Williams, PhD, and her team have pinpointed the specific area of chromosome 10 that causes AMD. It is a gene that controls an important protein in the back of the eye. When this protein is altered, it causes retinal death, abnormal blood vessel growth in the eye, and ultimately vision loss. The SCTM is concurrently developing a way to modulate Htra1 levels at the back of the eye and halt chromosome 10-directed AMD.

2012Biotechnology Partner

Dr. Hageman and colleagues found Voyant Biotherapeutics, LLC, a biotechnology company partnering with Moran to capitalize the commercialization of scientific discoveries made within the SCTM. Voyant mediates a partnership between the SCTM and Allergan, Inc. to expedite the pace of development of novel AMD therapeutics.

2014Therapy Targets

A massive SCTM/Allergan-led gene expression study generates about 9.2 billion data points and sheds new light on therapeutic targets for gene-directed AMD.

2018-2021—Clinical Trial in Sight for Chromosome 1-directed AMD

The SCTM develops a new therapy for chromosome 1-directed AMD, and pre-clinical testing produces viable drug candidates. Moran and a health care investment firm commit approximately $50 million to fund clinical trials for the new therapy. The SCTM team continues to pursue a therapy for the chromosome 10 form of AMD. It is anticipated that the disease process can be slowed, halted, or actually reversed if these drugs—if proven efficacious—are used at an early enough stage in disease progression.

2020—Utah Retinal Reading Center (UREAD)

Steffen Schmitz-Valckenberg, MD, establishes the Utah Retinal Reading Center (UREAD), which seeks to contribute to the characterization of manifestation and progression of ophthalmic diseases, focusing on the evaluation of treatment response to innovative therapeutic strategies. Using multimodal imaging technology, UREAD specializes in the standardized and systematic analysis (“grading”) of retinal imaging data within multicenter observational studies and interventional trials. UREAD plays a pivotoal role in the SCTM's development of AMD therapies.

2021—Chromosome 10-Directed AMD Elucidated 

The SCTM publishes a landmark study that details the molecular mechanisms causing AMD among patients with risk mutations on chromosome 10 (HTRA1 gene). The article demonstrates that, contrary to the dominant view, levels of the Htra1 protein in the eye region where AMD pathology develops are reduced in individuals carrying risk mutations on chromosome 10. This work indicates that increasing Htra1 levels in the back of the eye could be beneficial to slow down or prevent chromosome 10-directed AMD.