The eye’s photoreceptor cells are essential for vision because of their unique ability to convert light into visual signals. The loss of photoreceptors is at the root of many blinding eye diseases, including retinitis pigmentosa (RP), age-related macular degeneration (AMD), and Stargardt Disease – to name just a few.
Restoring photoreceptors therefore has tremendous therapeutic potential. Many research teams, around the world, are developing sight-restoring treatments that involve replacing damaged photoreceptors via stem cell transplantation.
Stem cell transplantation is not the only way to restore vision. Last week, an incredible discovery demonstrated that gene-editing can also restore sight.
The team, led by Kang Zhang from the University of California, San Diego, used the gene-editing tool, CRISPR, to change the genes that are expressed in rod photoreceptor cells. Specifically, they used CRISPR to turn off the genes Nrl and Nr2e3, which play an important role in the development of photoreceptors cells. There are two types of photoreceptors: rods and cones. Humans have approximately 6 million cones and about 120 million rods. Amazingly, the team observed that turning off these two genes in rods caused the cells to become cone photoreceptors. This “reprogramming” of rods into cones has powerful therapeutic potential, especially for retinitis pigmentosa (RP), which primarily involves the loss of rod photoreceptors.
Currently, there are no treatments for RP, which is an umbrella term for a group of inherited blinding eye diseases that are caused by mutations in more than 60 genes. Although there are different kinds of RP, all forms involve the death of rod photoreceptors, which are responsible for peripheral and night-vision. In contrast, cone photoreceptors are responsible for high-acuity, central vision. In RP, cones continue to function after the rods are gone, but ultimately begin to die toward the later stages of the disease.
To test if their reprogramming approach could work as a treatment for RP, the team studied two different animal models of RP. In both cases, the team demonstrated that reprogramming rod cells with CRISPR led to improved cone function, thereby reversing the development of RP and restoring visual function.
The team is optimistic that their approach could also work as a treatment for people living with RP because their proof-of-principle results in the laboratory are very encouraging. Although they are not able to test their approach in a clinical trial yet, they are certainly looking toward treatments in the future, especially because the need is so urgent.
This urgent need for new treatments and the fast-pace of promising vision research motivates the FFB’s Restore Vision 20/20 Initiative, which will fund sight-saving research with the greatest potential to move into a clinical trial.
About the study
Zhu, Jie et. al. 2017. Gene and mutation independent therapy via CRISPR-Cas9 mediated cellular reprogramming in rod photoreceptors. Cell Research doi: 10.1038/cr.2017.57
Image courtesy of National Center for Microscopy and Imaging Research, UC San Diego
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