{"id":24634,"date":"2019-05-30T10:13:55","date_gmt":"2019-05-30T16:13:55","guid":{"rendered":"https:\/\/www.uchealth.org\/today\/?p=24634"},"modified":"2024-12-24T09:17:58","modified_gmt":"2024-12-24T16:17:58","slug":"age-related-macular-degeneration-discoveries","status":"publish","type":"post","link":"https:\/\/www.uchealth.org\/today\/age-related-macular-degeneration-discoveries\/","title":{"rendered":"Patient registry holds promise for age-related macular degeneration discoveries"},"content":{"rendered":"
<\/div>
\"Image
Tara Churney, a senior profession research assistant for the Division of Ophthalmic Epidemiology, processes a blood sample for AMD registry\u2019s biorepository. Photo courtesy of Anne Lynch.<\/figcaption><\/figure>\n

Researchers on the UCHealth Anschutz Medical Campus believe that deepening repositories of electronic data could help shine a light on a disease that dooms millions of people to fading vision.<\/p>\n

The data comes from patients with age-related macular degeneration (AMD), which affects some 11 million people in the United States. The disease disrupts the functioning of the retina, the area at the back of the eye that is responsible for receiving light through photoreceptor cells. These cells convert the light to electrical impulses, which they pass along a cell network to the optic nerve and on to the brain. The disruption deteriorates vision and for many leads to blindness.<\/p>\n

In 2014, the University of Colorado School of Medicine\u2019s Department of Ophthalmology<\/a> launched the Division of Ophthalmic Epidemiology. The goal: probe the roots of age-related macular degeneration and spur research that could lead to new treatments for the disease. The division\u2019s research is bolstered with a $5 million gift that established the Frederic C. Hamilton Macular Diagnostics Center<\/a> at the Sue Anschutz-Rodgers Eye Center<\/a> and a $300,000 challenge grant to the Department of Ophthalmology from Research to Prevent Blindness<\/a>.<\/p>\n

Everybody into the data pool<\/strong><\/h3>\n

The Division of Ophthalmic Epidemiology laid the foundation for new age-related macular degeneration research in 2015 with a registry that today contains the medical records, imaging data and blood specimens of more than 1,000 patients with the disease. All of them receive their care at the UCHealth Eye Center. The registry also includes control data from patients who have cataracts but do not have AMD, said Dr. Anne Lynch, professor and director of the division, which includes a biostatistician, an epidemiologist and five professional research assistants.<\/p>\n

\"image
Dr. Anne Lynch directs the Division of Ophthalmic Epidemiology, which launched a registry of patients with age-related macular degeneration (AMD) in 2015. Photo by UCHealth.<\/figcaption><\/figure>\n

The registry recruitment of the past four years is ready to pay off, Lynch said.<\/p>\n

\u201cWe\u2019ve been very successful with our recruitment and now have the process streamlined,\u201d she said. \u201cWe are now at the point where we can do research.\u201d<\/p>\n

For example, Lynch pointed to a grant from the Macula Society<\/a> for proteomic studies that analyze the proteins expressed by cells and tissues in patients with early- or intermediate-stage, age-related macular degeneration. The Eye Center is also site for a National Eye Institute research grant that targets early-stage AMD patients. The Division of Ophthalmic Epidemiology and its partners have published or have under review several papers that examine the factors that may contribute to AMD, including an article in the journal Retina<\/em><\/a> published in 2018 that described the formation and goals of the registry as well as insights gleaned from it.<\/p>\n

In addition, the registry team now plans to collect a blood sample and images from patients once a year, a key to finding changes that offer clues to the progression of age-related macular degeneration.<\/p>\n

\u201cWe\u2019re looking for patients to study before they convert to the advanced form of the disease,\u201d Lynch said.<\/p>\n

Looking for light<\/strong><\/h3>\n

Those patients could shed new light on a disease that has so far remained stubbornly resistant to treatment. There are two types of age-related macular degeneration. About 10 percent have the \u201cwet\u201d form, which causes new blood vessels to grow abnormally in the retina and the retinal pigment epithelium (RPE), a covering of cells that nourishes and cleans the retina. Providers can treat wet AMD with injections that slow blood vessel growth. Geographic atrophy, or \u201cdry\u201d AMD, affects the vast majority of patients. Dry AMD causes cells to die in the retinal pigment epithelium. Without retinal pigment epithelium support, the photoreceptors atrophy and die, leading to vision loss and irreversible blindness.<\/p>\n

\"image
The detailed data in the patient registry is key to discovering therapies for AMD, says Dr. Naresh Mandava, chairman of the Department of Ophthalmology at the University of Colorado School of Medicine. Photo by UCHealth.<\/figcaption><\/figure>\n

There is as yet no treatment for the dry form of age-related macular degeneration and one isn\u2019t likely to come along without the kind of data the registry provides, said Dr. Naresh Mandava<\/a>, a retinal specialist and chair of the Department of Ophthalmology at CU.<\/p>\n

\u201cThe problem we have with drug therapies for AMD is that we have not yet identified the patient population that will rapidly progress,\u201d Mandava said.<\/p>\n

The registry vastly improves the odds of finding them, he added. Data from it could reveal, for example, unusual levels of specific proteins or molecules that accelerate the progression of the disease in some patients and not others. Such discoveries point to \u201cthe potential path of figuring out the cause of AMD\u201d and developing targeted therapies, Mandava said.<\/p>\n

\u201cIt\u2019s a true discovery opportunity,\u201d he said.<\/p>\n

Complementary research<\/strong><\/h3>\n
\"Image
Thuy Ton, a technologist at Exsera BioLabs, performs a test to measure complement proteins in blood samples. Such testing is shedding light on the contributors to age-related macular degeneration. Photo courtesy of Exsera BioLabs.<\/figcaption><\/figure>\n

The opportunities are more than speculation. Registry data is fueling research of the body\u2019s complement system in developing age-related macular degeneration. The complement system is a complex of proteins that helps the body fight infection, in large part by triggering inflammation. That\u2019s a good thing when the body is warding off microbial invaders but if the complement system for some reason malfunctions, the resulting cascade of inflammation-triggering proteins can damage tissue in various parts of the body including, potentially, the retina.<\/p>\n

\"image
Rheumatology Division Head Dr. V. Michael Holers works with the AMD patient registry to analyze proteins that may contribute to the disease. Photo by UCHealth.<\/figcaption><\/figure>\n

\u201cThe complement system is very pro-inflammatory,\u201d said Dr. V. Michael Holers<\/a>, head of the Division of Rheumatology<\/a> at the CU School of Medicine and an expert in the workings of the complement system. \u201cThe system itself doesn\u2019t discriminate between tissues when it causes damage. The target could be the joints, the eyes, the brain or the skin,\u201d Holers said.<\/p>\n

Research suggests that inflammation, improperly triggered, is the bridge from the complement system to age-related macular degeneration, Holers said. \u201cThe idea is that dysregulation of the complement system causes inflammation that kills cells in the back of the eye,\u201d he explained.<\/p>\n

Holers serves as clinical research consultant for the Division of Rheumatology\u2019s Exsera BioLabs, which specializes in measuring complement proteins in small volumes of liquid, including fluid from the eye. In his role with Exsera, Holers and his colleagues collaborate with Lynch and Mandava, analyzing panels of proteins in samples collected from patients in the age-related macular degeneration registry. The lab work has contributed to studies of AMD and other retinal eye diseases.<\/p>\n

Targeting inflammation<\/strong><\/h3>\n

Lynch, who acknowledged that genetics and other factors, notably cigarette smoking, are among many culprits in age-related macular degeneration, said the collaboration with Exsera has opened new research doors.<\/p>\n

\u201cGenetics doesn\u2019t tell the complete story of AMD,\u201d she said. \u201cWe are trying to see if AMD is a systemic disease. What we\u2019ve shown so far is that for sure these patients have markers of inflammation.\u201d<\/p>\n

That finding is only the beginning of a long road to offering patients hope. \u201cWe\u2019ve identified complement abnormalities and are working to refine our understanding of the complement system in AMD,\u201d Holers said. That effort is essential to one day developing therapies that block cell signaling that triggers the inflammation caused by specific complement proteins implicated in age-related macular degeneration.<\/p>\n

It requires a nuanced therapeutic approach, not an all-out assault on the system. As Holers put it, \u201cIn a complicated pathway like complements, where do you apply \u2018the hammer?\u2019\u201d But the therapeutic question is not only where to apply the hammer but when, he added.<\/p>\n

\"Image
Exsera Biolabs, part of the CU Division of Rheumatology, tests fluids from AMD registry patients for proteins that trigger inflammation. Photo courtesy of Exsera BioLabs.<\/figcaption><\/figure>\n

\u201cThe work with the registry has provided insights as to the appropriate therapeutic approach and at what time to introduce complement inhibitors during the very long course of AMD development,\u201d he said. \u201cIt points to the importance of using inhibitors much earlier than has been used to date.\u201d It also underscores the importance of using registry data to study important changes of many kinds in those patients who progress to the advanced form of age-related macular degeneration, as Lynch noted.<\/p>\n

Holers and Mandava also stressed the importance of using samples from human patients with the disease. Holers called the registry \u201cone of the fundamental tools that we use in modern biomedical research to make advances that are really directly related to patients. Traditionally we have used animal models, which are only approximations of the truth.\u201d<\/p>\n

Eying the mysteries of disease<\/strong><\/h3>\n

The registry is accomplishing the heavy data lifting necessary to make transformational clinical discoveries, Mandava said. There will be no short-term fixes for age-related macular degeneration, which in the years ahead is on course to affect millions of more people in a steadily aging population, he added.<\/p>\n

\u201cIt\u2019s not easy to take thousands of patients and follow them for five to 10 years,\u201d he said. \u201cAcademia has to do it.\u201d Without extensive registry data, he added, drug companies can\u2019t be expected to \u201ctake more long shots on goal\u201d with expensive trials with highly uncertain outcomes.<\/p>\n

The research from the registry, Mandava concluded, might develop relatively slowly but will strike at the most fundamental question of all: What is age-related macular degeneration?<\/p>\n

\u201cIf you don\u2019t know the discovery part, you\u2019ll never be successful in developing a therapy,\u201d Mandava said.<\/p>\n

 <\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

Researchers on the UCHealth Anschutz Medical Campus believe that deepening repositories of electronic data could help shine a light on a disease that dooms millions of people to fading vision. The data comes from patients with age-related macular degeneration (AMD), which affects some 11 million people in the United States. The disease disrupts the functioning […]<\/p>\n","protected":false},"author":2143,"featured_media":24638,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","footnotes":""},"categories":[5],"tags":[848,6763,3631],"class_list":["post-24634","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-innovative-care","tag-eye-care-ophthalmology","tag-retina","tag-uchealth-sue-anschutz-rodgers-eye-center"],"acf":[],"yoast_head":"\nAge-related macular degeneration discoveries find hope - UCHealth Today<\/title>\n<meta name=\"description\" content=\"Researchers at the CU explore the causes of age-related macular degeneration through data from more than 1,000 patients with the disease.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.uchealth.org\/today\/age-related-macular-degeneration-discoveries\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Patient registry holds promise for age-related macular degeneration discoveries\" \/>\n<meta property=\"og:description\" content=\"Researchers at the CU explore the causes of age-related macular degeneration through data from more than 1,000 patients with the disease.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.uchealth.org\/today\/age-related-macular-degeneration-discoveries\/\" \/>\n<meta property=\"og:site_name\" content=\"UCHealth Today\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/uchealthorg\/\" \/>\n<meta property=\"article:published_time\" content=\"2019-05-30T16:13:55+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-12-24T16:17:58+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/uchealth-wp-uploads.s3.amazonaws.com\/wp-content\/uploads\/sites\/6\/2019\/05\/30094819\/t-Macular-Degeneration6-.jpg\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Tyler Smith\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@uchealth\" \/>\n<meta name=\"twitter:site\" content=\"@uchealth\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Tyler Smith\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"8 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/www.uchealth.org\\\/today\\\/age-related-macular-degeneration-discoveries\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.uchealth.org\\\/today\\\/age-related-macular-degeneration-discoveries\\\/\"},\"author\":{\"name\":\"Tyler Smith\",\"@id\":\"https:\\\/\\\/www.uchealth.org\\\/today\\\/#\\\/schema\\\/person\\\/98c85c0e40c4933eedcec2cd054f349d\"},\"headline\":\"Patient registry holds promise for age-related macular degeneration discoveries\",\"datePublished\":\"2019-05-30T16:13:55+00:00\",\"dateModified\":\"2024-12-24T16:17:58+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/www.uchealth.org\\\/today\\\/age-related-macular-degeneration-discoveries\\\/\"},\"wordCount\":1658,\"publisher\":{\"@id\":\"https:\\\/\\\/www.uchealth.org\\\/today\\\/#organization\"},\"image\":{\"@id\":\"https:\\\/\\\/www.uchealth.org\\\/today\\\/age-related-macular-degeneration-discoveries\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/uchealth-wp-uploads.s3.amazonaws.com\\\/wp-content\\\/uploads\\\/sites\\\/6\\\/2019\\\/05\\\/30094819\\\/t-Macular-Degeneration6-.webp\",\"keywords\":[\"Eye care\",\"Retina\",\"UCHealth Sue Anschutz-Rodgers Eye Center\"],\"articleSection\":[\"Innovative care\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.uchealth.org\\\/today\\\/age-related-macular-degeneration-discoveries\\\/\",\"url\":\"https:\\\/\\\/www.uchealth.org\\\/today\\\/age-related-macular-degeneration-discoveries\\\/\",\"name\":\"Age-related macular degeneration discoveries find hope - 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