Congenital color vision deficiency affects over 200 million people worldwide, highlighting the significant demand for effective gene therapies targeting this condition.
The retina of the human eye contains photoreceptive cells called cones that allow color vision.
[1] These cones transduce the absorbed light into electrical information to be relayed through other cells along the phototransduction pathway, before reaching the visual cortex in the brain.
Although dichromacy poses few critical problems in daily life, a lack of access to many occupations (where color vision may be safety-critical) is a large disadvantage.
The severity of achromatopsia is much higher than dichromacy, not only in the lack of color vision, but also in co-occurring symptoms photophobia, nystagmus and poor visual acuity.
Using a replication-defective recombinant adeno-associated virus (rAAV) as a vector, the cDNA of the affected gene can be delivered to the cones at the back of the retina typically via subretinal injection.
The first retinal gene therapy to be approved by the FDA was Voretigene neparvovec in 2017, which treats Leber's congenital amaurosis, a genetic disorder that can lead to blindness.
These treatments also use subretinal injections of AAV vector and are therefore foundational to research in gene therapy for color blindness.
Recombinant AAV vector was to introduce the green fluorescent protein (GFP) gene in the cones of gerbils.
The methodology did not investigate novel color vision, though one respondent claimed to more easily interpret traffic lights.
They could also be replaced by intravitreal injections, which are significantly less invasive and can in theory be performed by a family doctor, but are less effective.
Mancuso et al. reported that the treated squirrel monkeys maintained 2 years of color vision after the treatment.
An editorial by J. Bennett points to Mancuso et al.'s use of an "unspecified postinjection corticosteroid therapy".
Contrary to this finding, Mancuso et al.’s success in conferring trichromacy to adult squirrel monkeys suggests that it is possible to adapt the preexisting circuit to allow greater acuity in color vision.
The researchers concluded that integrating the stimulus from the new photopigment as an adult was not analogous to vision loss following visual deprivation.
[16] Furthermore, even if gene therapy succeeds in converting incomplete colorblind individuals to trichromats, the degree of satisfaction among the subjects is unknown.
Technical complexity: Precisely delivering functional opsin genes to the retina without causing immune reactions or unintended side effects remains a significant hurdle.
Long-term efficacy: Ensuring the lasting effectiveness of gene therapy, as retinal cells have limited regeneration potential, is a key concern.