Findings from a study published in Current Biology, led by researchers from the Hebrew University of Jerusalem, evaluated the impact of a gene therapy to target CNGA3-achromatopsia (color blindness).
Start with CNGA3.
The CNGA3 gene provides instructions for making one part of the cone photoreceptor cyclic nucleotide-gated (CNG) channel, which are found solely in the cone photoreceptor cells within the retina.
And CNGA3-achromatopsia?
CNGA3-achromatopsia is a rare autosomal recessive condition in which patients only have rod photoreceptor-driven vision from birth.
As one of the few forms of color blindness that is caused by bi-allelic genetic mutations, this gene therapy offers an innovative approach to managing this congenital condition.
Now talk about the study.
Within a limited-scale study, four participants (three adults and a 7-year-old child) underwent monocular retinal gene augmentation therapy.
This involves delivering a functional copy of the CNGA3 gene (a cone-specific opsin promoter) to the subretinal region using a viral vector.
The goal was to have the intact CNGA3 gene correct the faulty genes in the rod cells.
How was visual perception measured?
Following this treatment therapy, the research team designed three consecutive experiments to measure participants’ ability to assess:
- Color lightness
- Color detection (defined as the ability to distinguish a colored stimulus from a grayscale one)
- Color saliency
Findings?
Shortly after treatment was administered, there were no significant changes in patients’ visual perception, though some cortical changes were noted by the researchers.
That’s it?
Not quite … in subsequent months, some participants began perceiving shades of gray differently compared to before the treatment.
Eventually, the patients consistently reported being able to see red objects against dark backgrounds.
Go on…
When contrasted to the patients’ untreated eyes—and while the perceived lightness of different colors was generally similar between the eyes—the patients could detect a colored stimulus only in their treated eyes.
Why was this the case?
The research team hypothesized that treated CNGA3-achromatopsia patients could perceive a stimulus’ color attribute, although in a form that is different and at limited capacity in comparison with patients with intact color vision.
Paint me a picture of how patients’ vision changed.?
The study participants explained that their visual perception of red stimuli “glows differently, shines, or appears on a different plane than the background” following treatment.
So is this the first study of its kind?
Sorta … but no.
The study authors compared this study to a similar animal model experiment conducted with sheep, wherein the gene therapy produced the complete restoration of color vision.
To note, rod cells in sheep with achromatopsia remained dormant.
How does this compare to humans?
As such, treating achromatopsia in humans proves more difficult because the activity of rod cells is necessary for night vision, causing interference with color perception during daylight hours.
Tell me more.
Lead author Ayelet McKyton, PhD, hypothesized that the active rod cells in the participants’ eyes could have hindered the signals created by the treated cone cells, consequently preventing restoration of color vision.
Simultaneously, the insensitivity of rod cells to red light wavelength may illustrate why the study participants could perceive red objects while still being unable to identify other colors.
Gotcha. Any treatment limitations?
Further studies are likely required to improve the treatment results.
For example, the study authors proposed that the suppression of rod cell activity could allow patients to partially restore color vision without reducing their daytime visual perception.
Take home.
According to the study authors, the results of this pioneering study demonstrate the potential for developing future gene therapy treatments to regain full functionality of color vision in patients with achromatopsia.
Next steps?
The research team will continue to monitor the study participants, which may lead to performing an additional round of treatment in the untreated eye with the hope of potentially improving their visual capabilities.