Blindness can onset at any point in life. The World Health Organisation has calculated that at least 2.2 billion people worldwide have a visual impairment, with at least 1 billion of these not being addressed. It is therefore imperative that further research takes place into the biological mechanisms that interplay during the loss of sight.
Most people would associate blindness as an age-related complication, but in fact blindness frequently can be genetic, or caused by a genetic disease. One of these is the genetic disease retinitis pigmentosa (RP), which currently affects one in four thousand people worldwide.
RP is caused by genetic mutation that initiates a cascade of events which eventually lead to a breakdown of the retina. This mutation is often passed down from parent to child. The retina lines the back of the eye and is composed of photoreceptors that respond to what we see, by transmitting information to the brain. Thus, a loss of these receptors with retinal breakdown causes vision loss.
This disease can be caused by mutation to over one hundred genes, with some causing a loss of vision quicker than others. Therefore, it seems that RP is a ticking time bomb, with early intervention required to slow its progression. In an attempt to battle this degeneration, a team at Wuhan University initiated an investigation, that has displayed promising evidence that we may be able to overcome RP by using genetic technologies.
This evidence showed that we could reverse RP’s effects in mice with a clever genetic tool – CRISPR technology. CRISPR works as an efficient pair of biologically-guided scissors that can remove any genetic sequence as desired. By removing mutated sequences, we can halt, and in some cases reverse, many diseases caused by genetic mutation.
In the investigation in Wuhan, the gene for PDE6β was targeted with CRISPR. The PDE6β gene plays a key part in photoreceptor transmission, in the sense that when mutated it becomes a cause of RP. In murine models, using CRISPR to snip out mutated regions of PDE6β restored vision in blind mice. This worked as the removal of mutated regions restored the function of PDE6β, leading to a longer lifespan of photoreceptors, increased photoreceptor transmission, and therefore improved vision.
Such an outcome is promising; if we could extend this principle to allow it to work successfully in humans, we could therefore have a cure for genetically caused blindness on our hands.
However, whilst the evidence explored is extremely hopeful, the authors acknowledge that further investigation is needed to prove this technique effective in human models. Kai Yao, a Professor at Wuhan University of Science and Technology, appreciates that finding a way to edit human retinal cells “would provide much more convincing evidence for the potential applications of these genome-editing tools in treating diseases”.
Though there lie many ethical concerns which currently make human genome editing illegal, it is possible that increased allowances in research for genomic technologies to be used in humans may support this advancement.
For now, however, the results achieved in mice are hopeful that we could indeed overcome blindness in humans with this mechanism, or one similar. With over one hundred genes causing RP in a wide range of cases, there are clearly more avenues to explore, at which we could implement genetic technologies to restore sight.
Image: Tiburi via Unsplash