Optogenetics: Can This Innovative Gene Therapy Treat Degenerative Retinal Disease and Possibly Restore Sight?

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A research group of Swiss and German scientists has restored vision to mice with a condition similar to retinitis pigmentosa (RP) by introducing engineered light-sensing proteins into their eyes, via a process known as optogenetics. Optogenetics is a still-experimental treatment for a variety of blinding retinal disorders that uses gene therapy to enable retinal and brain cells to respond to light.

According to the researchers, "… optogenetic gene therapy, which selectively introduces genes encoding light-sensitive proteins into surviving retinal cells to act as "replacement light sensors," holds considerable therapeutic potential: treatment is ambulant [i.e., enabling the person move about while being treated], long-lived, and has the theoretical potential to recover high-resolution vision across the entire visual field."

As explained by IFL Science, "When people lose light-sensing cells over a period of time … vision cells in deeper layers of the eye remain intact. While these cells cannot sense light, many of the signaling pathways are the same. It is in these deeper cells—known as retinal cells—that the researchers were able to insert the new light-sensing proteins, which can then use the already existing pathways to allow the cells to sense light."

This "proof of concept" research is in its earliest stages and has been conducted only with laboratory mice. Nevertheless, this concept shows promise for persons with RP, macular degeneration, and diabetic retinopathy.

About the Research

The study, entitled Restoring the ON Switch in Blind Retinas: Opto-mGluR6, a Next-Generation, Cell-Tailored Optogenetic Tool (explained below), has been published in the May 7, 2015 edition of PLoS Biology, an international, peer-reviewed, open-access online journal, published monthly by the Public Library of Science (PLoS). The PLoS is a non-profit organization of scientists and physicians who are committed to making the world's scientific and medical literature a freely available public resource.

The authors are Michiel van Wyk, Justyna Pielecka-Fortuna, Siegrid Löwel, and Sonja Kleinlogel, from the University of Bern, Switzerland and the University of Göttingen, Germany.

About Retinitis Pigmentosa

Retinitis pigmentosa (RP) is part of a large group of hereditary retinal conditions or dystrophies, involving one or several layers of the retina. RP occurs in approximately 1 in 4,000 people in the United States. At present, there is no cure.

A scene as it might be viewed by a person with retinitis pigmentosa

Most individuals with RP initially experience difficulty with night vision and in low light levels. Central (straight ahead) vision is usually retained until late in the course of the disease, while peripheral (or side) vision becomes progressively more constricted, resulting in "tunnel vision" (pictured above).

Primarily, the retinal rod cells – light-sensitive, specialized retinal receptor cells that activate at low light levels and provide night vision – are involved, but there may also be some involvement of the retinal cone cells, which function best in relatively bright light and provide color vision and greater visual acuity than do rod cells.

You can read more about retinitis pigmentosa research at What Is Retinitis Pigmentosa? by Frank J. Weinstock, MD, FACS at the VisionAware website.

More about the Research

From Optogenetics Restores Vision of Lab Mice, Could Soon Cure Acquired Blindness in Humans, via Medical Daily:

What our brains interpret as vision is actually the response of specialized cells in the eyes, known as retinal cells, to light stimuli. In those who were not born blind but rather acquired blindness over their lifetime, these retinal cells no longer function correctly because their light-sensing proteins are damaged. In the study, currently published in PLOS Biology, a team of researchers from the University of Berne in Switzerland attempted to replace the non-functioning cell parts with their own lab-engineered proteins, which they named Opto-mGluR6.

What sets Opto-mGluR6 apart from light-sensitive proteins occurring naturally in the eye is that these are particularly resilient to the effects of light. This means that their strength remains constant regardless of how much or how often they are hit with light. While Opto-mGluR6 is not the first lab-engineered light-sensitive protein, it differs from past models because it does not require a potentially damaging amount of light intensity in order to function.

Along with working under normal light stimuli, this novel protein also differs from past models because it is likely to be "invisible" to the host's immune system, iflscience reported. This invisibility is advantageous because it means that the host's body will likely not recognize the protein as an invading entity and unleash an attack.

The team introduced the engineered proteins into the eyes of blind mice using a modified virus. This method ensured that the protein could go directly to the surviving vision cells located deep within the eye. Opto-mGluR6 then replaced the no longer functioning photoreceptors and, in turn, restored the animals' vision. The results are promising and the team hopes to reproduce the effects in human subjects.

More about the Study from PLoS Biology

From the article Discussion:

An ideal therapy for patients suffering from photoreceptor degeneration will not only restore the light sensitivity of the retina but will (a) also function at environmental light intensities, (b) be physiologically compatible with the surviving inner retina, (c) conserve a natural range of retinal ganglion cell (RGC) trigger features, and (d) be devoid of toxic and immunogenic [i.e., generating an immune response] side effects.

[Editor's note: Retinal ganglion cells (RGCs), are neurons, or nervous system cells. They are located near the inner surface of the retina and give rise to optic nerve fibers that transmit information from the retina to several regions in the brain.]

All of this should be accomplished with a minimally invasive and safe clinical technology. Opto-mGluR6, which overcomes most shortfalls of existing optogenetic tools, meets most of these criteria and enhances the clinical feasibility of optogenetic vision recovery.

We showed that Opto-mGluR6 targeted to retinal [cells] of mice suffering from photoreceptor degeneration not only recovers light sensitivity in RGCs at moderate light intensities but also reestablishes diverse RGC light responses comprising ON, OFF, ON-OFF, sustained, and transient responses.

Additional Information


Topics:
Low Vision
In the News
Medical Updates
Clinical Trials
Diabetes and diabetic retinopathy
Macular Degeneration
Retinitis Pigmentosa
Stargardt Disease
Gene Therapy

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