Gene therapy for red–green colour blindness in adult primates

Abstract

It is often assumed that critical periods exist for the development of vision and other neural capabilities and that they end prior to adolescence. For example, it might be expected that gene therapy in adults with congenital vision disorders would be impossible. But experiments in adult spider monkeys who are normally red–green colour blind show that it is possible to add a third photopigment (human opsin) into some of their retinal cells by gene therapy. The monkeys acquire a new dimension of colour vision as a result. Not only does this suggest a possible therapy for a common congenital visual defect in humans (clinical trials are now under way), but also it demonstrates the extreme neuroplasticity of visual processing and points to possible routes by which trichromatic vision evolved. Red–green colour blindness is the most common single locus genetic disorder. Gene therapy is now used in adult monkeys, colour blind since birth, to provide the receptoral basis for trichromatic colour vision. Despite the expectation from classic visual deprivation experiments that neural connections established during development are incapable of processing an input not present from birth, treated monkeys displayed trichromatic colour vision behaviour. Red–green colour blindness, which results from the absence of either the long- (L) or the middle- (M) wavelength-sensitive visual photopigments, is the most common single locus genetic disorder. Here we explore the possibility of curing colour blindness using gene therapy in experiments on adult monkeys that had been colour blind since birth. A third type of cone pigment was added to dichromatic retinas, providing the receptoral basis for trichromatic colour vision. This opened a new avenue to explore the requirements for establishing the neural circuits for a new dimension of colour sensation. Classic visual deprivation experiments1 have led to the expectation that neural connections established during development would not appropriately process an input that was not present from birth. Therefore, it was believed that the treatment of congenital vision disorders would be ineffective unless administered to the very young. However, here we show that the addition of a third opsin in adult red–green colour-deficient primates was sufficient to produce trichromatic colour vision behaviour. Thus, trichromacy can arise from a single addition of a third cone class and it does not require an early developmental process. This provides a positive outlook for the potential of gene therapy to cure adult vision disorders.