Abstract
Abstract: :
Purpose: We have developed a model for the neural coding of color in which the cortical circuits for red–green color vision arise by hijacking the preexisting blue–yellow system. It predicts that adding a third cone pigment by gene therapy will be sufficient to transform an adult dichromat into a trichromat. We are testing this prediction by using gene therapy to deliver an L cone pigment gene to a subset of the M cones in a dichromatic squirrel monkey that has only M and S cones. These animals are an ideal model of human red–green colorblindness because the males are dichromatic, but females can be trichromatic. The objective of the gene therapy is to create a third cone type and determine whether the animal acquires a new sensory capacity, red–green color vision. A major question is whether the adult animal’s visual system will be able to respond to the new information provided by the transformed cones and thus allow him to discriminate colors that he was previously unable to differentiate. Methods: Color vision genotypes were determined by sequencing the X–chromosome pigment genes. Therapy was administered via sub–retinal injection of an adeno–associated viral vector that contains the human L–opsin gene, under the control of the L/M–opsin LCR and promoter. The goal is to take advantage of the capricious nature of viral infection, such that only a subset of cones near the injection site will be transduced. This will produce a retinal mosaic with two randomly interspersed cone types absorbing in the middle to long wavelengths, analogous to the normal human retina. To test the effects of this treatment on color vision behavior, a commercially available computerized color vision test, the Cambridge Colour Test, was adapted for use with the monkeys. Results: The Cambridge Colour Test has allowed us to measure the animals’ color vision with great precision. Discrimination thresholds versus gray were tested for 16 different colors distributed radially in color space. During pre–injection color vision testing, the monkeys failed to make red–green color discriminations as predicted from the analysis of their wild–type cone pigment genes. Conclusions: The technologies for genetically identifying dichromatic monkeys, administering a new cone pigment gene, and testing the animals’ color vision have been developed. These methods are being used to test a theory of color vision coding which predicts that a newly added cone type will expand color vision capacity in adults.
Keywords: color vision • color pigments and opsins • gene transfer/gene therapy