Gene therapy for red–green colour blindness in adult primates


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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: rAAV2/5 vector produced functional L-opsin in primate retina.
Figure 2: Pre-therapy colour vision and possible treatment outcomes.
Figure 3: Gene therapy produced trichromatic colour vision.


  1. 1

    Wiesel, T. N. & Hubel, D. H. Single-cell responses in striate cortex of kittens deprived of vision in one eye. J. Neurophysiol. 26, 1003–1017 (1963)

    CAS  Article  Google Scholar 

  2. 2

    Jacobs, G. H. A perspective on color vision in platyrrhine monkeys. Vision Res. 38, 3307–3313 (1998)

    CAS  Article  Google Scholar 

  3. 3

    Li, Q., Timmers, A. M., Guy, J., Pang, J. & Hauswirth, W. W. Cone-specific expression using a human red opsin promoter in recombinant AAV. Vision Res. 48, 332–338 (2007)

    Article  Google Scholar 

  4. 4

    Reffin, J. P., Astell, S. & Mollon, J. D. in Colour Vision Deficiencies X (eds Drum, B., Moreland, J. D. and Serra, A.) 69–76 (Kluwer Academic Publishers, 1991)

    Google Scholar 

  5. 5

    Regan, B. C., Reffin, J. P. & Mollon, J. D. Luminance noise and the rapid determination of discrimination ellipses in colour deficiency. Vision Res. 34, 1279–1299 (1994)

    CAS  Article  Google Scholar 

  6. 6

    Mancuso, K., Neitz, M. & Neitz, J. An adaptation of the Cambridge Colour Test for use with animals. Vis. Neurosci. 23, 695–701 (2006)

    Article  Google Scholar 

  7. 7

    Kuchenbecker, J. A., Sahay, M., Tait, D. M., Neitz, M. & Neitz, J. Topography of the long- to middle-wavelength sensitive cone ratio in the human retina assessed with a wide-field color multifocal electroretinogram. Vis. Neurosci. 25, 301–306 (2008)

    Article  Google Scholar 

  8. 8

    Mancuso, K. et al. Recombinant adeno-associated virus targets passenger gene expression to cones in primate retina. J. Opt. Soc. Am. A Opt. Image Sci. Vis. 24, 1411–1416 (2007)

    ADS  Article  Google Scholar 

  9. 9

    Nathans, J., Piantanida, T. P., Eddy, R. L., Shows, T. B. & Hogness, D. S. Molecular genetics of inherited variation in human color vision. Science 232, 203–210 (1986)

    ADS  CAS  Article  Google Scholar 

  10. 10

    Shapley, R. Specificity of cone connections in the retina and color vision. Focus on “Specificity of cone inputs to macaque retinal ganglion cells”. J. Neurophysiol. 95, 587–588 (2006)

    Article  Google Scholar 

  11. 11

    De Valois, R. L. & De Valois, K. K. A multi-stage color model. Vision Res. 33, 1053–1065 (1993)

    CAS  Article  Google Scholar 

  12. 12

    Jacobs, G. H., Williams, G. A., Cahill, H. & Nathans, J. Emergence of novel color vision in mice engineered to express a human cone photopigment. Science 315, 1723–1725 (2007)

    ADS  CAS  Article  Google Scholar 

  13. 13

    Makous, W. Comment on “emergence of novel color vision in mice engineered to express a human cone photopigment”. Science 318, 196 (2007)

    ADS  CAS  Article  Google Scholar 

  14. 14

    Maguire, A. M. et al. Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N. Engl. J. Med. 358, 2240–2248 (2008)

    CAS  Article  Google Scholar 

  15. 15

    Bainbridge, J. W. & Ali, R. R. Success in sight: the eyes have it! Ocular gene therapy trials for LCA look promising. Gene Ther. 15, 1191–1192 (2008)

    CAS  Article  Google Scholar 

  16. 16

    Cideciyan, A. V. et al. Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics. Proc. Natl Acad. Sci. USA 105, 15112–15117 (2008)

    ADS  CAS  Article  Google Scholar 

  17. 17

    Wang, Y. et al. A locus control region adjacent to the human red and green visual pigment genes. Neuron 9, 429–440 (1992)

    CAS  Article  Google Scholar 

  18. 18

    Mauck, M. C. et al. Longitudinal evaluation of expression of virally delivered transgenes in gerbil cone photoreceptors. Vis. Neurosci. 25, 273–282 (2008)

    Article  Google Scholar 

  19. 19

    Nathans, J., Thomas, D. & Hogness, D. S. Molecular genetics of human color vision: the genes encoding blue, green, and red pigments. Science 232, 193–202 (1986)

    ADS  CAS  Article  Google Scholar 

  20. 20

    Neitz, M., Neitz, J. & Jacobs, G. H. Spectral tuning of pigments underlying red-green color vision. Science 252, 971–974 (1991)

    ADS  CAS  Article  Google Scholar 

  21. 21

    Büning, H., Perabo, L., Coutelle, O., Quadt-Humme, S. & Hallek, M. Recent developments in adeno-associated virus vector technology. J. Gene Med. 10, 717–733 (2008)

    Article  Google Scholar 

Download references


This work was supported by the National Institutes of Health grants R01EY016861 (M.N.) and R01EY11123 (W.W.H.); Research Training Program in Vision Science Grant T32EY014537; NEI Core Grants for Vision Research P30EY01931, P30EY01730 and P30EY08571; the Harry J. Heeb Foundation, the Posner Foundation, the Macular Vision Research Foundation, the Foundation Fighting Blindness, Hope for Vision, and Research to Prevent Blindness. We would like to thank V. Chiodo, S. Boye, D. Conklyn, P. M. Summerfelt, K. Chmielewski and K. L. Gunther for technical assistance. J.N. is the Bishop Professor in Ophthalmology, M.N. is the Ray Hill Professor in Ophthalmology, and W.W.H. is Rybaczki-Bullard Professor of Ophthalmology.

Author Contributions Experiments and data analysis were performed by K.M., T.B.C., J.A.K., M.C.M., J.N. and M.N. Cone-specific expression of the gene therapy vector was developed and validated by Q.L., and W.W.H. constructed the vector and packaged it into adeno-associated virus and provided dosage guidance. All authors contributed to data interpretation. The manuscript was written by K.M., J.N. and M.N. and incorporates comments by all others.

Author information



Corresponding author

Correspondence to Jay Neitz.

Ethics declarations

Competing interests

W.W.H. and the University of Florida have a financial interest in the use of AAV therapies and own equity in the company, Applied Genetic Technologies Corporation Inc. (Alachua, Florida).

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Mancuso, K., Hauswirth, W., Li, Q. et al. Gene therapy for red–green colour blindness in adult primates. Nature 461, 784–787 (2009).

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.