Macular degeneration: Advances in stem cell and gene therapy

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.

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.