{"id":472552,"date":"2021-03-29T11:12:10","date_gmt":"2021-03-29T15:12:10","guid":{"rendered":"http:\/\/www.rochester.edu\/newscenter\/?p=472552"},"modified":"2025-11-19T07:59:34","modified_gmt":"2025-11-19T12:59:34","slug":"first-human-eye-lab-model-macular-degeneration-causes-472552","status":"publish","type":"post","link":"https:\/\/www.rochester.edu\/newscenter\/first-human-eye-lab-model-macular-degeneration-causes-472552\/","title":{"rendered":"First-ever lab model of human eye offers hope for macular degeneration patients"},"content":{"rendered":"<h2 style=\"width: 85%; font-weight: bold; line-height: 135%; margin-bottom: 0.5em;\">Rochester researchers say their breakthrough could lead to patient-specific treatments.<\/h2>\n<p>Age-related macular degeneration (AMD), which leads to a loss of central vision, is the most frequent cause of blindness in adults 50 years of age or older, affecting an <a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S2214109X13701451\">estimated 196 million people worldwide<\/a>. There is no cure, though treatment can slow the onset and preserve some vision.<\/p>\n<p>Recently, however, researchers at the <a href=\"https:\/\/www.rochester.edu\">University of Rochester<\/a> have made an important breakthrough in the quest for an AMD cure. Their first three-dimensional (3D) lab eye model mimics the part of the human retina affected in macular degeneration.<\/p>\n<p>Their model combines stem cell-derived retinal tissue and vascular networks from human patients with bioengineered synthetic materials in a three-dimensional \u201cmatrix.\u201d Notably, using patient-derived 3D retinal tissue allowed the researchers to investigate the underlying mechanisms involved in advanced neovascular macular degeneration, the <a href=\"https:\/\/www.brightfocus.org\/macular\/video\/what-wet-macular\">wet form<\/a> of macular degeneration, which is the more debilitating and blinding form of the disease.<\/p>\n<p>The researchers have also demonstrated that wet-AMD-related changes in their human retina model could be targeted with drugs.<\/p>\n<p>\u201cOnce we have validated this over a large sample, the next hope would be to develop rational drug therapies and potentially even test the efficacy of a specific drug to work for individual patients,\u201d says Ruchira Singh, an associate professor of ophthalmology at the University\u2019s <a href=\"https:\/\/www.urmc.rochester.edu\/eye-institute.aspx\">Flaum Eye Institute<\/a>.<\/p>\n<p>The lab of Danielle Benoit, professor of biomedical engineering and director of the <a href=\"https:\/\/www.hajim.rochester.edu\/matsci\/\">Materials Science Program<\/a>, engineered the synthetic materials for the matrix and helped configure it, as described in a <a href=\"https:\/\/www.cell.com\/cell-stem-cell\/fulltext\/S1934-5909(21)00056-4\">paper in <em>Cell Stem Cell<\/em><\/a>.<\/p>\n<p>Singh says the findings should help resolve a \u201chuge\u201d debate among researchers in the field who have been trying to determine whether:<\/p>\n<ul>\n<li>Defects in the retina itself are responsible for the disease (and if so, which parts of the retina are responsible); or<\/li>\n<li>The disease is caused by other \u201csystemic issues,\u201d for example, in blood supply.<\/li>\n<\/ul>\n<p>Their research points strongly to retinal defects as being responsible\u2014and in particular, to defects in an area called the retinal pigment epithelium (RPE), a pigmented cell layer that nourishes the retina\u2019s photoreceptor cells.<\/p>\n<figure id=\"attachment_472722\" aria-describedby=\"caption-attachment-472722\" style=\"width: 350px\" class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-472722 size-full\" src=\"https:\/\/www.rochester.edu\/newscenter\/wp-content\/uploads\/2021\/03\/inline-macular-degeneration-comparison.jpg\" alt=\"First illustration shows RPE cells, Bruch's mb, PEG layer, and vascular layer; second illustration shows the same but with a choroidal neovascularization-like pathology as well as drusen, or small yellow deposits of fatty protein indicating macular degeneration.\" width=\"350\" height=\"549\" \/><figcaption id=\"caption-attachment-472722\" class=\"wp-caption-text\">An illustration of the lab eye model that mimics the part of the human retina affected in macular degeneration. The model combines stem cell-derived retinal tissue and vascular networks from human patients with bioengineered synthetic materials in a 3D \u201cmatrix.\u201d (University of Rochester illustration \/ Michael Osadciw)<\/figcaption><\/figure>\n<h3><strong>Why animal models fail\u2014and a 3D eye model proved \u2018essential\u2019<\/strong><\/h3>\n<p>Two areas of the human eye are affected by AMD. They include the RPE and, beneath the RPE, an underlying support system called the choriocapillaris, composed largely of capillaries that feed the outer retina.<\/p>\n<p>Until now, researchers have relied largely on rodent models. But the anatomy and physiology of the human and rodent retinae are very different. According to Singh, it was essential to create \u201can in vitro human model of the choriocapillaris layer integrated with the RPE to get the entire complex that is affected by this disease.\u201d<\/p>\n<p>For example, in a previous study, Singh\u2019s lab used only a single retina cell type\u2014patient-derived retinal pigment epithelium (RPE)\u2014to show that symptoms of early and dry forms of AMD could be mimicked in culture, and could be solely caused by dysfunction in the RPE cells.\u00a0However, the role of the choriocapillaris layer had remained \u201ca mystery that nobody has ever been able to model in culture,\u201d she says.<\/p>\n<p>That\u2019s why it was so important to develop an in vitro and modular human eye model that could integrate a choriocapillaris layer with the RPE \u201cto get the entire complex that is affected by this disease, so that properties of each individual cell type can be controlled independently,\u201d Singh says.<\/p>\n<p>And that\u2019s why <a href=\"https:\/\/www.urmc.rochester.edu\/labs\/benoit.aspx\">Benoit\u2019s lab<\/a>, which specializes in creating synthetic hydrogels for cell culture, tissue engineering, and target drug delivery, was important.<\/p>\n<p>Benoit\u2019s lab engineered the 3D matrix in which the choriocapillaris could be safely placed and also \u201cproperly oriented in the overall vasculature,\u201d Benoit says. \u201cWe also facilitated the adhesion of the RPE cells within the model.\u00a0It was a small, but important contribution. A three-dimensional model was essential to describe the really amazing things that have been identified and discovered using this model.\u201d<\/p>\n<p>The findings offer a possible resolution to the debate over the causes of macular degeneration. The researchers now show for the first time that defects in RPE cells alone are sufficient to cause the disease. \u201cYou can have completely normal choriocapillaris, but if your RPE\u2019s are dysfunctional it will cause the choriocapillaris to dysfunction,\u201d Singh says.<\/p>\n<p>Similarly, using blood samples from patients with wet AMD in the human retina model, their data for the first time also shows that blood-derived factors from patients can independently contribute to the development and progression of wet AMD.<\/p>\n<p>The collaborations, Singh says, have succeeded in<\/p>\n<ul>\n<li>Creating an accurate human eye model of the RPE\/choriocapillaris complex<\/li>\n<li>Confirming that RPE and mesenchymal stem cells play a role in the development of the choriocapillaris layer<\/li>\n<li>Mimicking aspects of macular degeneration in the human eye model<\/li>\n<li>Understanding the role of specific cells types and blood-derived factors in the development of macular degeneration<\/li>\n<li>Targeting the disease, using a drug in a patient derived cell model<\/li>\n<\/ul>\n<h3><strong>World leadership in vision science<\/strong><\/h3>\n<p>The latest research by Singh and Benoit builds on the University of Rochester\u2019s long tradition as a world leader in vision science.<\/p>\n<p>In the 1990s, for example, <a href=\"https:\/\/www.urmc.rochester.edu\/people\/20026288-david-r-williams\">David Williams<\/a>, the William G. Allyn Professor of Medical Optics, and his group applied <a href=\"https:\/\/www.rochester.edu\/pr\/Review\/V75N2\/0306_williams.html\">adaptive optics<\/a>\u2014first used in telescopes to more clearly see through the Earth\u2019s atmosphere\u2014to image individual retinal cells, right down to single photoreceptors in the living human retina. The work of Williams and his team has had a far-reaching effect on procedures to improve vision and is applied throughout the world in Lasik procedures today.<\/p>\n<p>That legacy attracted both Singh and Benoit to Rochester, but so, too, did another factor: the proximity of the engineering and science departments and the Medical Center\u2014located across an avenue from one another\u2014and the chance to work together. Benoit says that proximity was a \u201ccritical\u201d factor in her decision to join the <a href=\"http:\/\/hajim.rochester.edu\/bme\/\">Department of Biomedical Engineering<\/a> in 2010. Singh says the opportunity to collaborate with Benoit was one of the main reasons she decided to join the Medical Center seven years ago.<\/p>\n<p>It\u2019s useful in forging other collaborations as well. Vision science at the University now involves a synergy of science, engineering and medicine across various departments including brain and cognitive sciences, neurobiology and anatomy, and ophthalmology, engaging about 100 Rochester faculty members. The <a href=\"https:\/\/www.cvs.rochester.edu\">Center for Visual Science<\/a>, and its <a href=\"https:\/\/aria.cvs.rochester.edu\/about.html#&amp;panel1-1\">ARIA lab<\/a>, directed by Williams, collaborates closely with the Medical Center\u2019s Flaum Eye Institute and is the hub of these collaborations.<\/p>\n<hr style=\"width: 50%;\" \/>\n<p><em>Funding support for their paper comes from both private foundations and the National Institutes of Health. The private foundations are BrightFocus Foundation, Foundation of Fighting Blindness, Knights Templar eye foundation, and the Retina Research Foundation and Research to Prevent Blindness.<\/em><\/p>\n<p><em>Other collaborators on the paper include:<\/em><\/p>\n<ul>\n<li><em>At the University of Rochester: Lead author Kannan V. Manian, Chad Galloway, Sonal Dalvi, Anthony A. Emanuel, Jared A. Mereness, Whitney Spencer, Lauren Winschel, Celia Soto, Yiming Li, Yuanhui Song, William DeMaria, and Mina Chung.<\/em><\/li>\n<li><em>At the University of Wisconsin: Akhilesh Kumar, Igor Slukvin, Michael P. Schwartz, and William L. Murphy.<\/em><\/li>\n<li><em>At the Cleveland Clinic Cole Eye Institute: Bela-Anand Apte<\/em><\/li>\n<\/ul>\n<hr \/>\n<h3><strong>Read more<\/strong><\/h3>\n<div class=\"large-up-3\">\n<div class=\"column\" style=\"padding-left: 0px;\"><a href=\"https:\/\/www.urmc.rochester.edu\/del-monte-neuroscience\/neuroscience-blog\/february-2021\/new-research-sheds-light-on-vision-loss-in-batten.aspx\"><img decoding=\"async\" style=\"margin-bottom: 10px;\" src=\"https:\/\/www.rochester.edu\/newscenter\/wp-content\/uploads\/2021\/03\/fea-young-girl-covers-eyes.jpg\" alt=\"Young blonde girl against black background wears white long sleeve shirt and covers her eyes.\" \/><strong>New research sheds light on vision loss in Batten Disease<\/strong><\/a><br \/>\n<span style=\"font-size: .9em;\">The mutation associated with the disease could potentially lead to degeneration of light sensing photoreceptor cells in the retina, and subsequent vision loss.<\/span><\/div>\n<div class=\"column\" style=\"padding-left: 0px;\"><a href=\"https:\/\/www.rochester.edu\/newscenter\/imaging-the-secret-lives-of-immune-cells-in-the-eye-455212\/\"><img decoding=\"async\" style=\"margin-bottom: 10px;\" src=\"https:\/\/www.rochester.edu\/newscenter\/wp-content\/uploads\/2020\/10\/2020_schallek-slide-2.jpg\" alt=\"microscopic immune cells escape a nearby blood vessel in response to inflammation.\" \/><strong>Imaging the secret lives of immune cells in the eye<\/strong><\/a><br \/>\n<span style=\"font-size: .9em;\">Rochester researchers demonstrate way to track the interactions of microscopic immune cells in a living eye without dyes or damage, a first for imaging science.<\/span><\/div>\n<div class=\"column\" style=\"padding-left: 0px;\"><a href=\"https:\/\/www.rochester.edu\/newscenter\/vision-expert-david-williams-receives-the-beckman-argyros-award-115572\/\"><img decoding=\"async\" style=\"margin-bottom: 10px;\" src=\"https:\/\/www.rochester.edu\/newscenter\/wp-content\/uploads\/2014\/04\/fea-david-williams-portrait.jpg\" alt=\"David Williams.\" \/><strong>Vision expert David Williams receives Beckman-Argyros Award<\/strong><\/a><br \/>\n<span style=\"font-size: .9em;\">Williams, an expert on human vision, pioneered the use of adaptive optics technologies for vision applications. <\/span><\/div>\n<\/div>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Rochester researchers&#8217; breakthrough could lead to patient-specific treatments for age-related macular degeneration, which leads to a loss of central vision.<\/p>\n","protected":false},"author":286,"featured_media":472832,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[42472,116],"tags":[22582,7716,18742,29502,20222,18632,37312],"class_list":["post-472552","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-health-medicine","category-sci-tech","tag-center-for-visual-science","tag-danielle-benoit","tag-department-of-biomedical-engineering","tag-featured-post-side","tag-flaum-eye-institute","tag-hajim-school-of-engineering-and-applied-sciences","tag-materials-science-program"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.5 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>First-ever lab model of human eye offers hope for macular degeneration patients<\/title>\n<meta name=\"description\" content=\"University of Rochester researchers&#039; 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