Gene Therapy for Eye Disease

Scheie Eye Institute, University of Pennsylvania
Medical illustration of genes. Gene therapy may one day be a viable treatment option for some eye diseases, including macular degeneration.
Learn about a recent gene therapy breakthrough and how that may open the door for new treatments for retinal diseases, including macular degeneration.

A Gene Therapy Breakthrough

There is a new breakthrough in gene therapy, with the FDA recently approving the first gene to be injected into people to treat a disease.

Scientists researching a form of inherited blindness in children called Leber’s congenital amaurosis recently had success in a clinical trial that improved the vision of children in the study. The trial was preceded by 30 years of research by Jean Bennett and her husband, Al Maguire, at the Scheie Eye Institute of the University of Pennsylvania, as well as other scientists at Penn and around the world.

The gene, which is called RPE65, is injected into the eye, under the retina, in an operating room procedure performed by Dr. Maguire. The gene enters retinal cells because it is packaged into a safe virus called adeno-associated virus (AAV).  Neither the naturally occurring AAV nor the genetically modified version designed to carry the RPE65 gene into people causes disease. On the contrary, the genetically modified AAV was able to significantly restore vision in blind children, enabling them to complete tasks such as walking through a maze without bumping into soft objects, or catching a ball.

Paving the Way for Other Eye Diseases

The retinal RPE65 gene therapy is a breakthrough that will pave the way for gene therapies treating a number of other retinal diseases, including age-related macular degeneration (AMD), retinitis pigmentosa, choroideremia, and others.  Now that a safe and effective technique has been established for delivering a gene into the retina, additional genes can now be delivered to the retina in the same way and tested for efficacy and safety in clinical trials.

Challenges do remain, however. Some genes, such as the one causing Stargardt’s hereditary maculopathy (an inherited disorder of the macula that typically causes vision loss during childhood or adolescence), are too large to be carried into the retina by the AAV virus, so other approaches must be developed. For example, a clinical trial is evaluating another type of virus, called lentivirus, which can carry larger genes.  For some complex diseases, such as AMD, it is not as clear which genes will protect vision.


In a phase I clinical trial for wet AMD, a gene therapy called “Retinostat,” delivered by injection under the retina, has proven safe. It also continues to make proteins that inhibit abnormal blood vessel growth, called angiostatin and endostatin, for at least one year after injection. These proteins were measured in fluid samples taken from inside the eye. Future clinical trials will likely test whether Retinostat can block the growth of harmful blood vessels in patients with wet AMD and diabetic retinopathy.

Another gene therapy approach to wet AMD is using a virus to carry a helpful gene into the eye. One company uses an injection under the retina of the AAV virus carrying a gene, called sFLT, which creates a vascular endothelial growth factor (VEGF) blocker. VEGF is also the target of the currently approved wet AMD drugs brolucizumab (Beovu®), aflibercept (Eylea®), ranibizumab (Lucentis®), and bevacizumab (Avastin®). In a phase I trial, the therapy was safe and appeared to nearly eliminate the need for additional treatments over a one-year period. A second company uses an injection into the eye instead of under the retina using the same virus carrying the sFLT gene, which has the potential to be safer and more convenient.


Gene therapy for dry AMD is not yet as far along as that for wet AMD. However, it is likely to be helpful after further research and development. Genetic, biochemical, and cell biology studies have identified a number of potential approaches to treat dry AMD, such as anti-inflammatory, anti-oxidant, anti-cholesterol, and anti-cell-death approaches. Some of these have proven effective in gene therapy studies in mice.

A Word of Caution

A potential downside of gene therapy is that, in most cases, it will not be possible to turn off the therapy once it is delivered into the eye. The cells that receive the therapeutic genes will continue to express them for years. Therefore, clinical trials are very important to determine the long-term safety of this approach. Fortunately, the pioneering gene therapy trials for Leber’s congenital amaurosis do not have long-term safety issues, and are restoring some vision in children who were born blind!


This content was first posted on: July 27, 2018

The information provided here is a public service of the BrightFocus Foundation and should not in any way substitute for personalized advice of a qualified healthcare professional; it is not intended to constitute medical advice. Please consult your physician for personalized medical advice. BrightFocus Foundation does not endorse any medical product, therapy, or resources mentioned or listed in this article. All medications and supplements should only be taken under medical supervision. Also, although we make every effort to keep the medical information on our website updated, we cannot guarantee that the posted information reflects the most up-to-date research.

These articles do not imply an endorsement of BrightFocus by the author or their institution, nor do they imply an endorsement of the institution or author by BrightFocus.

Some of the content may be adapted from other sources, which will be clearly identified within the article.

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