Macular degeneration: Advances in stem cell and gene therapy
January 9, 2023
This article is co-authored by John Hulleman, Ph.D.
Dry age-related macular degeneration (AMD) is a complex condition that distorts a patient’s vision. Left untreated, the disease can develop into wet AMD, which is more severe. Wet AMD causes retinal leaking and bleeding, vision changes, and eye damage that cannot be reversed.
The International Agency for the Prevention of Blindness estimates that in 2020 approximately 196 million people worldwide had AMD, and that number is expected to increase to 288 million by 2040. Today, there is no cure for AMD. Drugs that target a substance in the blood called vascular endothelial growth factor (VEGF) can be effective temporarily – patients will need frequent medication injections in the eye.
But promising research at UT Southwestern and the National Institutes of Health (NIH) is focused on improving current treatments and paving the way for new therapies. We anticipate that this research will be a springboard for the treatment of AMD and other age-related retinal diseases. Two of the most exciting areas of study today are gene therapy and stem cell therapy.
Gene therapy for AMD
UT Southwestern is conducting pre-clinical studies developing potential gene therapies that target mechanisms of disease apart from VEGF. This approach could reduce the need for patients to have frequent drug injections in their eyes. In fact, the goal is to find out how gene therapy can slow or even prevent AMD by targeting novel disease pathways, or how a disease develops.
For example, one study involves introducing into the retina an adeno-associated virus (AAV) – a clinically approved, genetically altered, nontoxic virus. The AAV carries a specific DNA sequence that reprograms retinal cells and reestablishes defective cellular pathways, such as those involved in inflammation. This might help slow the progression of AMD and more aggressive eye conditions that cause rapid loss of retinal function at an early age.
Some of our research uses mouse models to try to replicate certain aspects of AMD, although this is difficult with some disease characteristics. Preliminary studies suggest we can fine-tune signaling in mouse retinas to restore a balanced eye environment. In the future, we expect that similar gene therapies will be available to treat AMD and other complex eye diseases.
Related article: When AMD, Parkinson's and Alzheimer's affect the eyes
Stem cell therapy for AMD
The NIH is conducting trials in which researchers are using (and possibly editing) patient-derived induced pluripotent stem cells (iPS cells) in their laboratories. In other words, they are using stem cells to grow new retinal cells that have the identical genetic makeup of a patient.
Theoretically, iPS-derived retinal cells could be transplanted into a patient with AMD to improve their condition, and researchers at the National Eye Institute have already begun clinical trials to test this approach.
Recent advancements have allowed researchers to try to create eye-like organoids that are structurally similar to fully developed human eyes. We can even replicate some diseases in the laboratory using these models. In fact, recent research from the University of Wisconsin has demonstrated that retinal organoids can generate cone photoreceptors (those primarily affected in AMD) that respond appropriately to light. This research could one day help us examine eye conditions and test potential treatments without risk to human patients.
Retinal injury and disease recovery research
Today, research in AMD is focused on the basics: What causes it? How does it affect the eye? Can macular degeneration be reversed? How can we improve current therapies?
A constant focus is understanding how diseases cause retinal injury and how the retina tries to recover. This information will eventually help us develop therapies to minimize injury and maximize recovery.
Currently, we are using focused light to replicate retinal injury in the laboratory. Then, we study how it changes the cells and genes to better understand how we can intervene and preserve vision. This approach may even allow us to generate therapies that are not disease-specific, which could make preventive therapies and treatment more widely accessible to patients.
There is no single breakthrough in AMD research that will cover all the questions and opportunities for prevention and treatment. Today and in the future, the key to successful retinal disease management will continue to rely on a combination of diligent research, technological advancements, and expert care from a team of AMD and retinal disease specialists.
To find out whether you or a loved one might benefit from a team approach to AMD or retinal disease care, call 214-645-2020 or request an appointment online.