Scientists have taken another important step toward restoring vision in people with certain inherited forms of blindness. In a study published in the New England Journal of Medicine, researchers at the University of Pittsburgh School of Medicine and international collaborators showed that an experimental, optogenetics-based treatment was safely administered to 10 patients and improved visual function in some participants when used in combination with a specially designed visual stimulation device.

The retina, a thin layer of tissue at the back of the eye that captures light and sends visual information to the brain, is part of the central nervous system and thus, unlike many other tissues in the body, has a limited ability to repair itself.

Targeting vision loss across genetic causes

Retinitis pigmentosa (RP), which destroys light-sensing cells in the retina, affects more than 1.5 million people worldwide. At onset, patients first notice impaired night vision, then impaired peripheral vision that gradually worsens over time and can ultimately lead to severe vision loss or blindness.

“Retinitis pigmentosa can result from a mutation in any one of more than 100 distinct genes, so it presents an extraordinary challenge,” said José-Alain Sahel, distinguished professor and chair of the Department of Ophthalmology at Pitt, director of the UPMC Vision Institute and first and co-corresponding author of the study.

While in recent years Sahel and others have made strides in stopping and even reversing other progressive blinding diseases using gene therapies that target specific disease-causing mutations, RP requires an outside-the-box approach.

“Developing a separate treatment for every genetic cause of retinitis pigmentosa is proving tremendously difficult and costly. While we continue working on correcting specific gene defects, our goal is to develop a way to restore visual function regardless of which gene caused the disease,” said Sahel.

Pairing light-sensitive cells with specialized goggles

In optogenetics, scientists alter cells to produce light-sensing proteins, which they are working to modulate for a variety of experimental uses. In this study, the team delivered a gene that produces a light-sensing protein known as ChrimsonR into surviving retinal ganglion cells via a single injection into the eye.

The protein is then put into action with a visual prosthetic system. The user wears specialized goggles with a built-in camera that sends visual information to a portable processor. The processor, in turn, converts the information into patterns of light. A projector within the glasses sends these patterns of light back to the eye at specific wavelengths designed to activate ChrimsonR in the modified retinal cells.

Early gains in light and object detection

The researchers administered the optogenetic treatment to 10 people with advanced retinitis pigmentosa who were legally blind with little or no remaining vision. In this small, early-stage trial, the team found encouraging results in tests of the treatment’s safety.

Most eye-related side effects were mild or moderate and included temporary inflammation and short-lived increases in eye pressure.

After treatment, seven of the 10 participants had improved light sensitivity, and six made gains large enough to be considered clinically meaningful. While the treatment did not restore normal vision or the ability to read, some participants became better able to detect when an object was present, determine where it was located and reach toward it accurately while using the goggles.

The team also tested whether visual information was reaching the brain. Using electroencephalography (EEG), researchers led by Marlene Behrmann, professor of ophthalmology at Pitt, found evidence that visual signals reached and were processed by the visual cortex when participants viewed objects. Four participants showed consistent improvements across multiple real-world visual tasks over months to years of testing.

Broader prospects for vision restoration

“These results show that even in people with profound vision loss, the visual system retains a remarkable capacity to process new information,” said Sahel.

“Potentially, the approach could also help patients with other blinding diseases in which the eye’s light-sensing cells have been lost, but other retinal cells—especially retinal ganglion cells—remain viable. Many of these patients currently have few or no treatment options.”

The study builds on a landmark Nature Medicine paper published in 2021, the first report of partial recovery of visual function in a blind patient following optogenetic therapy and the first-ever clinical application of optogenetics in medicine.

Last month, Sahel and his longtime collaborator, Botond Roska, of the Institute of Molecular and Clinical Ophthalmology Basel, who is also a corresponding author of the current study, received the António Champalimaud Vision Award, the largest award in the field, for their contribution to vision restoration research.

The findings of the new study highlight one of several promising and complementary strategies the team is pursuing to restore vision in patients with end-stage retinal disease.

Last year, Sahel was senior author of a New England Journal of Medicine article describing the ability to restore vision using an implanted prosthetic in patients with end-stage, age-related macular degeneration. The technology, known as PRIMA, has since received permission from the European Union to be marketed for clinical use within many European countries.

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