Abstract

Human trichromatic vision is based on three classes of cones: L, M, and S (long-, middle-, and short-wavelength sensitive, respectively). Individuals can have more than one M and/or more than one L pigment gene on the X chromosome along with an S pigment gene on chromosome 7. In some people the X-linked pigment gene array can include polymorphic variants that encode multiple, spectrally distinct cone photopigment subtypes. A single-cell, polymerase chain reaction approach was used to examine visual pigment gene expression in individual human cone cells and identify them as L or M. The ratio of L:M pigment gene expression was assayed in homogenized retinal tissues taken from the same eyes. Results indicate that there is a close correspondence between the cone ratio determined from counting single cells and the L:M pigment mRNA ratio estimated from homogenized pieces of retina. The results also show that the different pigment genes in one array are often expressed at very different levels, giving rise to unequal numbers of L and M cones. Expression of only one photopigment gene was detected in each cone cell. However, individual males can have more than the classically described three spectrally distinct cone types in their retinas.

© 2000 Optical Society of America

Full Article  |  PDF Article

References

  • View by:
  • |
  • |
  • |

  1. T. Young, “On the theory of light and colours,” Philos. Trans. R. Soc. London 92, 12–48 (1802).
    [CrossRef]
  2. J. Nathans, D. Thomas, D. S. Hogness, “Molecular genetics of human color vision: the genes encoding blue, green, and red pigments,” Science 232, 193–202 (1986).
    [CrossRef] [PubMed]
  3. M. Neitz, J. Neitz, “Numbers and ratios of visual pigment genes for normal red–green color vision,” Science 267, 1013–1016 (1995).
    [CrossRef] [PubMed]
  4. M. Neitz, J. Neitz, A. Grishok, “Polymorphism in the number of genes encoding long-wavelength sensitive cone pigments among males with normal color vision,” Vision Res. 35, 2395–2407 (1995).
    [CrossRef] [PubMed]
  5. S. Wolf, L. Sharpe, H. Knau, B. Wissinger, “Numbers and ratios of X-chromosomal-linked opsin genes,” Vision Res. 38, 3227–3231 (1998).
    [CrossRef]
  6. T. Yamaguchi, A. G. Motulsky, S. S. Deeb, “Visual pigment gene structure and expression in the human retinae,” Hum. Mol. Genet. 6, 981–990 (1997).
    [CrossRef] [PubMed]
  7. T. Hayashi, A. G. Motulsky, S. S. Deeb, “Position of a ‘green–red’ hybrid gene in the visual pigment array determines colour-vision phenotype,” Nature Genet. 22, 90–93 (1999).
    [CrossRef]
  8. M. Neitz, J. Neitz, G. H. Jacobs, “Spectral tuning of pigments underlying red–green color vision,” Science 252, 971–974 (1991).
    [CrossRef] [PubMed]
  9. J. Neitz, M. Neitz, G. H. Jacobs, “More than three different cone pigments among people with normal color vision,” Vision Res. 33, 117–122 (1993).
    [CrossRef] [PubMed]
  10. J. Winderickx, D. T. Lindsey, E. Sanocki, D. Y. Teller, A. G. Motulsky, S. S. Deeb, “Polymorphism in red photopigment underlies variation in colour matching,” Nature 356, 431–433 (1992).
    [CrossRef] [PubMed]
  11. J. Winderickx, L. Battisti, A. G. Motulsky, S. S. Deeb, “Selective expression of human X chromosome-linked green opsin genes,” Proc. Natl. Acad. Sci. USA 89, 9710–9714 (1992).
    [CrossRef] [PubMed]
  12. S. D. Balding, S. A. Sjoberg, J. Neitz, M. Neitz, “Pigment gene expression in protan color vision defects,” Vision Res. 38, 3359–3364 (1998).
    [CrossRef]
  13. S. A. Sjoberg, M. Neitz, S. D. Balding, J. Neitz, “L-cone pigment genes expressed in normal colour vision,” Vision Res. 38, 3213–3219 (1998).
    [CrossRef]
  14. S. A. Hagstrom, J. Neitz, M. Neitz, “Variations in cone populations for red–green color vision examined by analysis of mRNA,” NeuroReport 9, 1963–1967 (1998).
    [CrossRef] [PubMed]
  15. S. A. Hagstrom, J. Neitz, M. Neitz, “Four different cone types in a human eye identified from mRNA in individual photoreceptors,” Invest. Ophthalmol. Visual Sci. Suppl. 36, S1054 (1995).
  16. S. A. Hagstrom, “Characterization of cone pigment genes expressed in human retina and in individual cone photoreceptors,” Ph.D. dissertation (Medical College of Wisconsin, Milwaukee, Wis., 1996).
  17. S. A. Hagstrom, J. Neitz, M. Neitz, “Ratio of M/L pigment gene expression decreases with retinal eccentricity,” in Colour Vision Deficiencies XIII, C. R. Cavonius, ed. (Kluwer Academic, Dordrecht, The Netherlands, 1997), pp. 59–66.
  18. M. Neitz, T. W. Kraft, J. Neitz, “Expression of L cone pigment gene subtypes in females,” Vision Res. 38, 3221–3225 (1998).
    [CrossRef]
  19. C. A. Curcio, K. A. Allen, K. R. Sloan, C. L. Lerea, J. B. Hurley, I. B. Klock, A. H. Milam, “Distribution and morphology of human cone photoreceptors stained with anti-blue opsin,” J. Comp. Neurol. 312, 610–624 (1991).
    [CrossRef] [PubMed]
  20. A. Szel, P. Rohlich, A. Caffe, T. Van Veen, “Distribution of cone photoreceptors in the mammalian retina,” Microsc. Res. Tech. 35, 445–462 (1996).
    [CrossRef] [PubMed]
  21. Y. Wang, P. Smallwood, M. Cowan, D. Blesh, A. Lawler, J. Nathans, “Mutually exclusive expression of human red and green visual pigment-reporter transgenes occurs at high frequency in murine cone photoreceptors,” Proc. Natl. Acad. Sci. USA 96, 5251–5256 (1999).
    [CrossRef] [PubMed]
  22. M. Xiao, A. Hendrickson, “Developmental expression patterns of cone opsins in human photoreceptors,” Invest. Ophthalmol. Visual Sci. Suppl. 40, S457 (1999).
  23. C. M. Cicerone, J. L. Nerger, “The relative numbers of long-wavelength-sensitive to middle-wavelength-sensitive cones in the human fovea centralis,” Vision Res. 29, 115–128 (1989).
    [CrossRef] [PubMed]
  24. H. J. A. Dartnall, J. K. Bowmaker, J. D. Mollon, “Human visual pigments: microspectrophotometric results from the eye of seven persons,” Proc. R. Soc. London Ser. B 220, 115–130 (1983).
    [CrossRef]
  25. J. L. Nerger, C. M. Cicerone, “The ratio of L cones to M cones in the human parafoveal retina,” Vision Res. 32, 879–888 (1992).
    [CrossRef] [PubMed]
  26. J. Pokorny, V. C. Smith, M. F. Wesner, “Variability in cone populations and implications,” in From Pigments to Perception, A. Valberg, B. B. Lee, eds. (Plenum, New York, 1991).
  27. A. Roorda, D. R. Williams, “The arrangement of three cone classes in the living human eye,” Nature 397, 520–522 (1999).
    [CrossRef] [PubMed]
  28. J. Neitz, M. Neitz, P. M. Kainz, “Visual pigment gene structure and the severity of color vision defects,” Science 274, 801–804 (1996).
    [CrossRef] [PubMed]

1999

T. Hayashi, A. G. Motulsky, S. S. Deeb, “Position of a ‘green–red’ hybrid gene in the visual pigment array determines colour-vision phenotype,” Nature Genet. 22, 90–93 (1999).
[CrossRef]

Y. Wang, P. Smallwood, M. Cowan, D. Blesh, A. Lawler, J. Nathans, “Mutually exclusive expression of human red and green visual pigment-reporter transgenes occurs at high frequency in murine cone photoreceptors,” Proc. Natl. Acad. Sci. USA 96, 5251–5256 (1999).
[CrossRef] [PubMed]

M. Xiao, A. Hendrickson, “Developmental expression patterns of cone opsins in human photoreceptors,” Invest. Ophthalmol. Visual Sci. Suppl. 40, S457 (1999).

A. Roorda, D. R. Williams, “The arrangement of three cone classes in the living human eye,” Nature 397, 520–522 (1999).
[CrossRef] [PubMed]

1998

S. Wolf, L. Sharpe, H. Knau, B. Wissinger, “Numbers and ratios of X-chromosomal-linked opsin genes,” Vision Res. 38, 3227–3231 (1998).
[CrossRef]

S. D. Balding, S. A. Sjoberg, J. Neitz, M. Neitz, “Pigment gene expression in protan color vision defects,” Vision Res. 38, 3359–3364 (1998).
[CrossRef]

S. A. Sjoberg, M. Neitz, S. D. Balding, J. Neitz, “L-cone pigment genes expressed in normal colour vision,” Vision Res. 38, 3213–3219 (1998).
[CrossRef]

S. A. Hagstrom, J. Neitz, M. Neitz, “Variations in cone populations for red–green color vision examined by analysis of mRNA,” NeuroReport 9, 1963–1967 (1998).
[CrossRef] [PubMed]

M. Neitz, T. W. Kraft, J. Neitz, “Expression of L cone pigment gene subtypes in females,” Vision Res. 38, 3221–3225 (1998).
[CrossRef]

1997

T. Yamaguchi, A. G. Motulsky, S. S. Deeb, “Visual pigment gene structure and expression in the human retinae,” Hum. Mol. Genet. 6, 981–990 (1997).
[CrossRef] [PubMed]

1996

J. Neitz, M. Neitz, P. M. Kainz, “Visual pigment gene structure and the severity of color vision defects,” Science 274, 801–804 (1996).
[CrossRef] [PubMed]

A. Szel, P. Rohlich, A. Caffe, T. Van Veen, “Distribution of cone photoreceptors in the mammalian retina,” Microsc. Res. Tech. 35, 445–462 (1996).
[CrossRef] [PubMed]

1995

M. Neitz, J. Neitz, “Numbers and ratios of visual pigment genes for normal red–green color vision,” Science 267, 1013–1016 (1995).
[CrossRef] [PubMed]

M. Neitz, J. Neitz, A. Grishok, “Polymorphism in the number of genes encoding long-wavelength sensitive cone pigments among males with normal color vision,” Vision Res. 35, 2395–2407 (1995).
[CrossRef] [PubMed]

S. A. Hagstrom, J. Neitz, M. Neitz, “Four different cone types in a human eye identified from mRNA in individual photoreceptors,” Invest. Ophthalmol. Visual Sci. Suppl. 36, S1054 (1995).

1993

J. Neitz, M. Neitz, G. H. Jacobs, “More than three different cone pigments among people with normal color vision,” Vision Res. 33, 117–122 (1993).
[CrossRef] [PubMed]

1992

J. Winderickx, D. T. Lindsey, E. Sanocki, D. Y. Teller, A. G. Motulsky, S. S. Deeb, “Polymorphism in red photopigment underlies variation in colour matching,” Nature 356, 431–433 (1992).
[CrossRef] [PubMed]

J. Winderickx, L. Battisti, A. G. Motulsky, S. S. Deeb, “Selective expression of human X chromosome-linked green opsin genes,” Proc. Natl. Acad. Sci. USA 89, 9710–9714 (1992).
[CrossRef] [PubMed]

J. L. Nerger, C. M. Cicerone, “The ratio of L cones to M cones in the human parafoveal retina,” Vision Res. 32, 879–888 (1992).
[CrossRef] [PubMed]

1991

C. A. Curcio, K. A. Allen, K. R. Sloan, C. L. Lerea, J. B. Hurley, I. B. Klock, A. H. Milam, “Distribution and morphology of human cone photoreceptors stained with anti-blue opsin,” J. Comp. Neurol. 312, 610–624 (1991).
[CrossRef] [PubMed]

M. Neitz, J. Neitz, G. H. Jacobs, “Spectral tuning of pigments underlying red–green color vision,” Science 252, 971–974 (1991).
[CrossRef] [PubMed]

1989

C. M. Cicerone, J. L. Nerger, “The relative numbers of long-wavelength-sensitive to middle-wavelength-sensitive cones in the human fovea centralis,” Vision Res. 29, 115–128 (1989).
[CrossRef] [PubMed]

1986

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

1983

H. J. A. Dartnall, J. K. Bowmaker, J. D. Mollon, “Human visual pigments: microspectrophotometric results from the eye of seven persons,” Proc. R. Soc. London Ser. B 220, 115–130 (1983).
[CrossRef]

1802

T. Young, “On the theory of light and colours,” Philos. Trans. R. Soc. London 92, 12–48 (1802).
[CrossRef]

Allen, K. A.

C. A. Curcio, K. A. Allen, K. R. Sloan, C. L. Lerea, J. B. Hurley, I. B. Klock, A. H. Milam, “Distribution and morphology of human cone photoreceptors stained with anti-blue opsin,” J. Comp. Neurol. 312, 610–624 (1991).
[CrossRef] [PubMed]

Balding, S. D.

S. D. Balding, S. A. Sjoberg, J. Neitz, M. Neitz, “Pigment gene expression in protan color vision defects,” Vision Res. 38, 3359–3364 (1998).
[CrossRef]

S. A. Sjoberg, M. Neitz, S. D. Balding, J. Neitz, “L-cone pigment genes expressed in normal colour vision,” Vision Res. 38, 3213–3219 (1998).
[CrossRef]

Battisti, L.

J. Winderickx, L. Battisti, A. G. Motulsky, S. S. Deeb, “Selective expression of human X chromosome-linked green opsin genes,” Proc. Natl. Acad. Sci. USA 89, 9710–9714 (1992).
[CrossRef] [PubMed]

Blesh, D.

Y. Wang, P. Smallwood, M. Cowan, D. Blesh, A. Lawler, J. Nathans, “Mutually exclusive expression of human red and green visual pigment-reporter transgenes occurs at high frequency in murine cone photoreceptors,” Proc. Natl. Acad. Sci. USA 96, 5251–5256 (1999).
[CrossRef] [PubMed]

Bowmaker, J. K.

H. J. A. Dartnall, J. K. Bowmaker, J. D. Mollon, “Human visual pigments: microspectrophotometric results from the eye of seven persons,” Proc. R. Soc. London Ser. B 220, 115–130 (1983).
[CrossRef]

Caffe, A.

A. Szel, P. Rohlich, A. Caffe, T. Van Veen, “Distribution of cone photoreceptors in the mammalian retina,” Microsc. Res. Tech. 35, 445–462 (1996).
[CrossRef] [PubMed]

Cicerone, C. M.

J. L. Nerger, C. M. Cicerone, “The ratio of L cones to M cones in the human parafoveal retina,” Vision Res. 32, 879–888 (1992).
[CrossRef] [PubMed]

C. M. Cicerone, J. L. Nerger, “The relative numbers of long-wavelength-sensitive to middle-wavelength-sensitive cones in the human fovea centralis,” Vision Res. 29, 115–128 (1989).
[CrossRef] [PubMed]

Cowan, M.

Y. Wang, P. Smallwood, M. Cowan, D. Blesh, A. Lawler, J. Nathans, “Mutually exclusive expression of human red and green visual pigment-reporter transgenes occurs at high frequency in murine cone photoreceptors,” Proc. Natl. Acad. Sci. USA 96, 5251–5256 (1999).
[CrossRef] [PubMed]

Curcio, C. A.

C. A. Curcio, K. A. Allen, K. R. Sloan, C. L. Lerea, J. B. Hurley, I. B. Klock, A. H. Milam, “Distribution and morphology of human cone photoreceptors stained with anti-blue opsin,” J. Comp. Neurol. 312, 610–624 (1991).
[CrossRef] [PubMed]

Dartnall, H. J. A.

H. J. A. Dartnall, J. K. Bowmaker, J. D. Mollon, “Human visual pigments: microspectrophotometric results from the eye of seven persons,” Proc. R. Soc. London Ser. B 220, 115–130 (1983).
[CrossRef]

Deeb, S. S.

T. Hayashi, A. G. Motulsky, S. S. Deeb, “Position of a ‘green–red’ hybrid gene in the visual pigment array determines colour-vision phenotype,” Nature Genet. 22, 90–93 (1999).
[CrossRef]

T. Yamaguchi, A. G. Motulsky, S. S. Deeb, “Visual pigment gene structure and expression in the human retinae,” Hum. Mol. Genet. 6, 981–990 (1997).
[CrossRef] [PubMed]

J. Winderickx, L. Battisti, A. G. Motulsky, S. S. Deeb, “Selective expression of human X chromosome-linked green opsin genes,” Proc. Natl. Acad. Sci. USA 89, 9710–9714 (1992).
[CrossRef] [PubMed]

J. Winderickx, D. T. Lindsey, E. Sanocki, D. Y. Teller, A. G. Motulsky, S. S. Deeb, “Polymorphism in red photopigment underlies variation in colour matching,” Nature 356, 431–433 (1992).
[CrossRef] [PubMed]

Grishok, A.

M. Neitz, J. Neitz, A. Grishok, “Polymorphism in the number of genes encoding long-wavelength sensitive cone pigments among males with normal color vision,” Vision Res. 35, 2395–2407 (1995).
[CrossRef] [PubMed]

Hagstrom, S. A.

S. A. Hagstrom, J. Neitz, M. Neitz, “Variations in cone populations for red–green color vision examined by analysis of mRNA,” NeuroReport 9, 1963–1967 (1998).
[CrossRef] [PubMed]

S. A. Hagstrom, J. Neitz, M. Neitz, “Four different cone types in a human eye identified from mRNA in individual photoreceptors,” Invest. Ophthalmol. Visual Sci. Suppl. 36, S1054 (1995).

S. A. Hagstrom, J. Neitz, M. Neitz, “Ratio of M/L pigment gene expression decreases with retinal eccentricity,” in Colour Vision Deficiencies XIII, C. R. Cavonius, ed. (Kluwer Academic, Dordrecht, The Netherlands, 1997), pp. 59–66.

S. A. Hagstrom, “Characterization of cone pigment genes expressed in human retina and in individual cone photoreceptors,” Ph.D. dissertation (Medical College of Wisconsin, Milwaukee, Wis., 1996).

Hayashi, T.

T. Hayashi, A. G. Motulsky, S. S. Deeb, “Position of a ‘green–red’ hybrid gene in the visual pigment array determines colour-vision phenotype,” Nature Genet. 22, 90–93 (1999).
[CrossRef]

Hendrickson, A.

M. Xiao, A. Hendrickson, “Developmental expression patterns of cone opsins in human photoreceptors,” Invest. Ophthalmol. Visual Sci. Suppl. 40, S457 (1999).

Hogness, D. S.

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

Hurley, J. B.

C. A. Curcio, K. A. Allen, K. R. Sloan, C. L. Lerea, J. B. Hurley, I. B. Klock, A. H. Milam, “Distribution and morphology of human cone photoreceptors stained with anti-blue opsin,” J. Comp. Neurol. 312, 610–624 (1991).
[CrossRef] [PubMed]

Jacobs, G. H.

J. Neitz, M. Neitz, G. H. Jacobs, “More than three different cone pigments among people with normal color vision,” Vision Res. 33, 117–122 (1993).
[CrossRef] [PubMed]

M. Neitz, J. Neitz, G. H. Jacobs, “Spectral tuning of pigments underlying red–green color vision,” Science 252, 971–974 (1991).
[CrossRef] [PubMed]

Kainz, P. M.

J. Neitz, M. Neitz, P. M. Kainz, “Visual pigment gene structure and the severity of color vision defects,” Science 274, 801–804 (1996).
[CrossRef] [PubMed]

Klock, I. B.

C. A. Curcio, K. A. Allen, K. R. Sloan, C. L. Lerea, J. B. Hurley, I. B. Klock, A. H. Milam, “Distribution and morphology of human cone photoreceptors stained with anti-blue opsin,” J. Comp. Neurol. 312, 610–624 (1991).
[CrossRef] [PubMed]

Knau, H.

S. Wolf, L. Sharpe, H. Knau, B. Wissinger, “Numbers and ratios of X-chromosomal-linked opsin genes,” Vision Res. 38, 3227–3231 (1998).
[CrossRef]

Kraft, T. W.

M. Neitz, T. W. Kraft, J. Neitz, “Expression of L cone pigment gene subtypes in females,” Vision Res. 38, 3221–3225 (1998).
[CrossRef]

Lawler, A.

Y. Wang, P. Smallwood, M. Cowan, D. Blesh, A. Lawler, J. Nathans, “Mutually exclusive expression of human red and green visual pigment-reporter transgenes occurs at high frequency in murine cone photoreceptors,” Proc. Natl. Acad. Sci. USA 96, 5251–5256 (1999).
[CrossRef] [PubMed]

Lerea, C. L.

C. A. Curcio, K. A. Allen, K. R. Sloan, C. L. Lerea, J. B. Hurley, I. B. Klock, A. H. Milam, “Distribution and morphology of human cone photoreceptors stained with anti-blue opsin,” J. Comp. Neurol. 312, 610–624 (1991).
[CrossRef] [PubMed]

Lindsey, D. T.

J. Winderickx, D. T. Lindsey, E. Sanocki, D. Y. Teller, A. G. Motulsky, S. S. Deeb, “Polymorphism in red photopigment underlies variation in colour matching,” Nature 356, 431–433 (1992).
[CrossRef] [PubMed]

Milam, A. H.

C. A. Curcio, K. A. Allen, K. R. Sloan, C. L. Lerea, J. B. Hurley, I. B. Klock, A. H. Milam, “Distribution and morphology of human cone photoreceptors stained with anti-blue opsin,” J. Comp. Neurol. 312, 610–624 (1991).
[CrossRef] [PubMed]

Mollon, J. D.

H. J. A. Dartnall, J. K. Bowmaker, J. D. Mollon, “Human visual pigments: microspectrophotometric results from the eye of seven persons,” Proc. R. Soc. London Ser. B 220, 115–130 (1983).
[CrossRef]

Motulsky, A. G.

T. Hayashi, A. G. Motulsky, S. S. Deeb, “Position of a ‘green–red’ hybrid gene in the visual pigment array determines colour-vision phenotype,” Nature Genet. 22, 90–93 (1999).
[CrossRef]

T. Yamaguchi, A. G. Motulsky, S. S. Deeb, “Visual pigment gene structure and expression in the human retinae,” Hum. Mol. Genet. 6, 981–990 (1997).
[CrossRef] [PubMed]

J. Winderickx, L. Battisti, A. G. Motulsky, S. S. Deeb, “Selective expression of human X chromosome-linked green opsin genes,” Proc. Natl. Acad. Sci. USA 89, 9710–9714 (1992).
[CrossRef] [PubMed]

J. Winderickx, D. T. Lindsey, E. Sanocki, D. Y. Teller, A. G. Motulsky, S. S. Deeb, “Polymorphism in red photopigment underlies variation in colour matching,” Nature 356, 431–433 (1992).
[CrossRef] [PubMed]

Nathans, J.

Y. Wang, P. Smallwood, M. Cowan, D. Blesh, A. Lawler, J. Nathans, “Mutually exclusive expression of human red and green visual pigment-reporter transgenes occurs at high frequency in murine cone photoreceptors,” Proc. Natl. Acad. Sci. USA 96, 5251–5256 (1999).
[CrossRef] [PubMed]

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

Neitz, J.

S. D. Balding, S. A. Sjoberg, J. Neitz, M. Neitz, “Pigment gene expression in protan color vision defects,” Vision Res. 38, 3359–3364 (1998).
[CrossRef]

S. A. Hagstrom, J. Neitz, M. Neitz, “Variations in cone populations for red–green color vision examined by analysis of mRNA,” NeuroReport 9, 1963–1967 (1998).
[CrossRef] [PubMed]

S. A. Sjoberg, M. Neitz, S. D. Balding, J. Neitz, “L-cone pigment genes expressed in normal colour vision,” Vision Res. 38, 3213–3219 (1998).
[CrossRef]

M. Neitz, T. W. Kraft, J. Neitz, “Expression of L cone pigment gene subtypes in females,” Vision Res. 38, 3221–3225 (1998).
[CrossRef]

J. Neitz, M. Neitz, P. M. Kainz, “Visual pigment gene structure and the severity of color vision defects,” Science 274, 801–804 (1996).
[CrossRef] [PubMed]

M. Neitz, J. Neitz, “Numbers and ratios of visual pigment genes for normal red–green color vision,” Science 267, 1013–1016 (1995).
[CrossRef] [PubMed]

S. A. Hagstrom, J. Neitz, M. Neitz, “Four different cone types in a human eye identified from mRNA in individual photoreceptors,” Invest. Ophthalmol. Visual Sci. Suppl. 36, S1054 (1995).

M. Neitz, J. Neitz, A. Grishok, “Polymorphism in the number of genes encoding long-wavelength sensitive cone pigments among males with normal color vision,” Vision Res. 35, 2395–2407 (1995).
[CrossRef] [PubMed]

J. Neitz, M. Neitz, G. H. Jacobs, “More than three different cone pigments among people with normal color vision,” Vision Res. 33, 117–122 (1993).
[CrossRef] [PubMed]

M. Neitz, J. Neitz, G. H. Jacobs, “Spectral tuning of pigments underlying red–green color vision,” Science 252, 971–974 (1991).
[CrossRef] [PubMed]

S. A. Hagstrom, J. Neitz, M. Neitz, “Ratio of M/L pigment gene expression decreases with retinal eccentricity,” in Colour Vision Deficiencies XIII, C. R. Cavonius, ed. (Kluwer Academic, Dordrecht, The Netherlands, 1997), pp. 59–66.

Neitz, M.

S. A. Sjoberg, M. Neitz, S. D. Balding, J. Neitz, “L-cone pigment genes expressed in normal colour vision,” Vision Res. 38, 3213–3219 (1998).
[CrossRef]

S. A. Hagstrom, J. Neitz, M. Neitz, “Variations in cone populations for red–green color vision examined by analysis of mRNA,” NeuroReport 9, 1963–1967 (1998).
[CrossRef] [PubMed]

M. Neitz, T. W. Kraft, J. Neitz, “Expression of L cone pigment gene subtypes in females,” Vision Res. 38, 3221–3225 (1998).
[CrossRef]

S. D. Balding, S. A. Sjoberg, J. Neitz, M. Neitz, “Pigment gene expression in protan color vision defects,” Vision Res. 38, 3359–3364 (1998).
[CrossRef]

J. Neitz, M. Neitz, P. M. Kainz, “Visual pigment gene structure and the severity of color vision defects,” Science 274, 801–804 (1996).
[CrossRef] [PubMed]

M. Neitz, J. Neitz, “Numbers and ratios of visual pigment genes for normal red–green color vision,” Science 267, 1013–1016 (1995).
[CrossRef] [PubMed]

S. A. Hagstrom, J. Neitz, M. Neitz, “Four different cone types in a human eye identified from mRNA in individual photoreceptors,” Invest. Ophthalmol. Visual Sci. Suppl. 36, S1054 (1995).

M. Neitz, J. Neitz, A. Grishok, “Polymorphism in the number of genes encoding long-wavelength sensitive cone pigments among males with normal color vision,” Vision Res. 35, 2395–2407 (1995).
[CrossRef] [PubMed]

J. Neitz, M. Neitz, G. H. Jacobs, “More than three different cone pigments among people with normal color vision,” Vision Res. 33, 117–122 (1993).
[CrossRef] [PubMed]

M. Neitz, J. Neitz, G. H. Jacobs, “Spectral tuning of pigments underlying red–green color vision,” Science 252, 971–974 (1991).
[CrossRef] [PubMed]

S. A. Hagstrom, J. Neitz, M. Neitz, “Ratio of M/L pigment gene expression decreases with retinal eccentricity,” in Colour Vision Deficiencies XIII, C. R. Cavonius, ed. (Kluwer Academic, Dordrecht, The Netherlands, 1997), pp. 59–66.

Nerger, J. L.

J. L. Nerger, C. M. Cicerone, “The ratio of L cones to M cones in the human parafoveal retina,” Vision Res. 32, 879–888 (1992).
[CrossRef] [PubMed]

C. M. Cicerone, J. L. Nerger, “The relative numbers of long-wavelength-sensitive to middle-wavelength-sensitive cones in the human fovea centralis,” Vision Res. 29, 115–128 (1989).
[CrossRef] [PubMed]

Pokorny, J.

J. Pokorny, V. C. Smith, M. F. Wesner, “Variability in cone populations and implications,” in From Pigments to Perception, A. Valberg, B. B. Lee, eds. (Plenum, New York, 1991).

Rohlich, P.

A. Szel, P. Rohlich, A. Caffe, T. Van Veen, “Distribution of cone photoreceptors in the mammalian retina,” Microsc. Res. Tech. 35, 445–462 (1996).
[CrossRef] [PubMed]

Roorda, A.

A. Roorda, D. R. Williams, “The arrangement of three cone classes in the living human eye,” Nature 397, 520–522 (1999).
[CrossRef] [PubMed]

Sanocki, E.

J. Winderickx, D. T. Lindsey, E. Sanocki, D. Y. Teller, A. G. Motulsky, S. S. Deeb, “Polymorphism in red photopigment underlies variation in colour matching,” Nature 356, 431–433 (1992).
[CrossRef] [PubMed]

Sharpe, L.

S. Wolf, L. Sharpe, H. Knau, B. Wissinger, “Numbers and ratios of X-chromosomal-linked opsin genes,” Vision Res. 38, 3227–3231 (1998).
[CrossRef]

Sjoberg, S. A.

S. A. Sjoberg, M. Neitz, S. D. Balding, J. Neitz, “L-cone pigment genes expressed in normal colour vision,” Vision Res. 38, 3213–3219 (1998).
[CrossRef]

S. D. Balding, S. A. Sjoberg, J. Neitz, M. Neitz, “Pigment gene expression in protan color vision defects,” Vision Res. 38, 3359–3364 (1998).
[CrossRef]

Sloan, K. R.

C. A. Curcio, K. A. Allen, K. R. Sloan, C. L. Lerea, J. B. Hurley, I. B. Klock, A. H. Milam, “Distribution and morphology of human cone photoreceptors stained with anti-blue opsin,” J. Comp. Neurol. 312, 610–624 (1991).
[CrossRef] [PubMed]

Smallwood, P.

Y. Wang, P. Smallwood, M. Cowan, D. Blesh, A. Lawler, J. Nathans, “Mutually exclusive expression of human red and green visual pigment-reporter transgenes occurs at high frequency in murine cone photoreceptors,” Proc. Natl. Acad. Sci. USA 96, 5251–5256 (1999).
[CrossRef] [PubMed]

Smith, V. C.

J. Pokorny, V. C. Smith, M. F. Wesner, “Variability in cone populations and implications,” in From Pigments to Perception, A. Valberg, B. B. Lee, eds. (Plenum, New York, 1991).

Szel, A.

A. Szel, P. Rohlich, A. Caffe, T. Van Veen, “Distribution of cone photoreceptors in the mammalian retina,” Microsc. Res. Tech. 35, 445–462 (1996).
[CrossRef] [PubMed]

Teller, D. Y.

J. Winderickx, D. T. Lindsey, E. Sanocki, D. Y. Teller, A. G. Motulsky, S. S. Deeb, “Polymorphism in red photopigment underlies variation in colour matching,” Nature 356, 431–433 (1992).
[CrossRef] [PubMed]

Thomas, D.

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

Van Veen, T.

A. Szel, P. Rohlich, A. Caffe, T. Van Veen, “Distribution of cone photoreceptors in the mammalian retina,” Microsc. Res. Tech. 35, 445–462 (1996).
[CrossRef] [PubMed]

Wang, Y.

Y. Wang, P. Smallwood, M. Cowan, D. Blesh, A. Lawler, J. Nathans, “Mutually exclusive expression of human red and green visual pigment-reporter transgenes occurs at high frequency in murine cone photoreceptors,” Proc. Natl. Acad. Sci. USA 96, 5251–5256 (1999).
[CrossRef] [PubMed]

Wesner, M. F.

J. Pokorny, V. C. Smith, M. F. Wesner, “Variability in cone populations and implications,” in From Pigments to Perception, A. Valberg, B. B. Lee, eds. (Plenum, New York, 1991).

Williams, D. R.

A. Roorda, D. R. Williams, “The arrangement of three cone classes in the living human eye,” Nature 397, 520–522 (1999).
[CrossRef] [PubMed]

Winderickx, J.

J. Winderickx, L. Battisti, A. G. Motulsky, S. S. Deeb, “Selective expression of human X chromosome-linked green opsin genes,” Proc. Natl. Acad. Sci. USA 89, 9710–9714 (1992).
[CrossRef] [PubMed]

J. Winderickx, D. T. Lindsey, E. Sanocki, D. Y. Teller, A. G. Motulsky, S. S. Deeb, “Polymorphism in red photopigment underlies variation in colour matching,” Nature 356, 431–433 (1992).
[CrossRef] [PubMed]

Wissinger, B.

S. Wolf, L. Sharpe, H. Knau, B. Wissinger, “Numbers and ratios of X-chromosomal-linked opsin genes,” Vision Res. 38, 3227–3231 (1998).
[CrossRef]

Wolf, S.

S. Wolf, L. Sharpe, H. Knau, B. Wissinger, “Numbers and ratios of X-chromosomal-linked opsin genes,” Vision Res. 38, 3227–3231 (1998).
[CrossRef]

Xiao, M.

M. Xiao, A. Hendrickson, “Developmental expression patterns of cone opsins in human photoreceptors,” Invest. Ophthalmol. Visual Sci. Suppl. 40, S457 (1999).

Yamaguchi, T.

T. Yamaguchi, A. G. Motulsky, S. S. Deeb, “Visual pigment gene structure and expression in the human retinae,” Hum. Mol. Genet. 6, 981–990 (1997).
[CrossRef] [PubMed]

Young, T.

T. Young, “On the theory of light and colours,” Philos. Trans. R. Soc. London 92, 12–48 (1802).
[CrossRef]

Hum. Mol. Genet.

T. Yamaguchi, A. G. Motulsky, S. S. Deeb, “Visual pigment gene structure and expression in the human retinae,” Hum. Mol. Genet. 6, 981–990 (1997).
[CrossRef] [PubMed]

Invest. Ophthalmol. Visual Sci. Suppl.

S. A. Hagstrom, J. Neitz, M. Neitz, “Four different cone types in a human eye identified from mRNA in individual photoreceptors,” Invest. Ophthalmol. Visual Sci. Suppl. 36, S1054 (1995).

M. Xiao, A. Hendrickson, “Developmental expression patterns of cone opsins in human photoreceptors,” Invest. Ophthalmol. Visual Sci. Suppl. 40, S457 (1999).

J. Comp. Neurol.

C. A. Curcio, K. A. Allen, K. R. Sloan, C. L. Lerea, J. B. Hurley, I. B. Klock, A. H. Milam, “Distribution and morphology of human cone photoreceptors stained with anti-blue opsin,” J. Comp. Neurol. 312, 610–624 (1991).
[CrossRef] [PubMed]

Microsc. Res. Tech.

A. Szel, P. Rohlich, A. Caffe, T. Van Veen, “Distribution of cone photoreceptors in the mammalian retina,” Microsc. Res. Tech. 35, 445–462 (1996).
[CrossRef] [PubMed]

Nature

A. Roorda, D. R. Williams, “The arrangement of three cone classes in the living human eye,” Nature 397, 520–522 (1999).
[CrossRef] [PubMed]

J. Winderickx, D. T. Lindsey, E. Sanocki, D. Y. Teller, A. G. Motulsky, S. S. Deeb, “Polymorphism in red photopigment underlies variation in colour matching,” Nature 356, 431–433 (1992).
[CrossRef] [PubMed]

Nature Genet.

T. Hayashi, A. G. Motulsky, S. S. Deeb, “Position of a ‘green–red’ hybrid gene in the visual pigment array determines colour-vision phenotype,” Nature Genet. 22, 90–93 (1999).
[CrossRef]

NeuroReport

S. A. Hagstrom, J. Neitz, M. Neitz, “Variations in cone populations for red–green color vision examined by analysis of mRNA,” NeuroReport 9, 1963–1967 (1998).
[CrossRef] [PubMed]

Philos. Trans. R. Soc. London

T. Young, “On the theory of light and colours,” Philos. Trans. R. Soc. London 92, 12–48 (1802).
[CrossRef]

Proc. Natl. Acad. Sci. USA

J. Winderickx, L. Battisti, A. G. Motulsky, S. S. Deeb, “Selective expression of human X chromosome-linked green opsin genes,” Proc. Natl. Acad. Sci. USA 89, 9710–9714 (1992).
[CrossRef] [PubMed]

Y. Wang, P. Smallwood, M. Cowan, D. Blesh, A. Lawler, J. Nathans, “Mutually exclusive expression of human red and green visual pigment-reporter transgenes occurs at high frequency in murine cone photoreceptors,” Proc. Natl. Acad. Sci. USA 96, 5251–5256 (1999).
[CrossRef] [PubMed]

Proc. R. Soc. London Ser. B

H. J. A. Dartnall, J. K. Bowmaker, J. D. Mollon, “Human visual pigments: microspectrophotometric results from the eye of seven persons,” Proc. R. Soc. London Ser. B 220, 115–130 (1983).
[CrossRef]

Science

J. Neitz, M. Neitz, P. M. Kainz, “Visual pigment gene structure and the severity of color vision defects,” Science 274, 801–804 (1996).
[CrossRef] [PubMed]

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

M. Neitz, J. Neitz, “Numbers and ratios of visual pigment genes for normal red–green color vision,” Science 267, 1013–1016 (1995).
[CrossRef] [PubMed]

M. Neitz, J. Neitz, G. H. Jacobs, “Spectral tuning of pigments underlying red–green color vision,” Science 252, 971–974 (1991).
[CrossRef] [PubMed]

Vision Res.

J. Neitz, M. Neitz, G. H. Jacobs, “More than three different cone pigments among people with normal color vision,” Vision Res. 33, 117–122 (1993).
[CrossRef] [PubMed]

M. Neitz, J. Neitz, A. Grishok, “Polymorphism in the number of genes encoding long-wavelength sensitive cone pigments among males with normal color vision,” Vision Res. 35, 2395–2407 (1995).
[CrossRef] [PubMed]

S. Wolf, L. Sharpe, H. Knau, B. Wissinger, “Numbers and ratios of X-chromosomal-linked opsin genes,” Vision Res. 38, 3227–3231 (1998).
[CrossRef]

S. D. Balding, S. A. Sjoberg, J. Neitz, M. Neitz, “Pigment gene expression in protan color vision defects,” Vision Res. 38, 3359–3364 (1998).
[CrossRef]

S. A. Sjoberg, M. Neitz, S. D. Balding, J. Neitz, “L-cone pigment genes expressed in normal colour vision,” Vision Res. 38, 3213–3219 (1998).
[CrossRef]

M. Neitz, T. W. Kraft, J. Neitz, “Expression of L cone pigment gene subtypes in females,” Vision Res. 38, 3221–3225 (1998).
[CrossRef]

J. L. Nerger, C. M. Cicerone, “The ratio of L cones to M cones in the human parafoveal retina,” Vision Res. 32, 879–888 (1992).
[CrossRef] [PubMed]

C. M. Cicerone, J. L. Nerger, “The relative numbers of long-wavelength-sensitive to middle-wavelength-sensitive cones in the human fovea centralis,” Vision Res. 29, 115–128 (1989).
[CrossRef] [PubMed]

Other

J. Pokorny, V. C. Smith, M. F. Wesner, “Variability in cone populations and implications,” in From Pigments to Perception, A. Valberg, B. B. Lee, eds. (Plenum, New York, 1991).

S. A. Hagstrom, “Characterization of cone pigment genes expressed in human retina and in individual cone photoreceptors,” Ph.D. dissertation (Medical College of Wisconsin, Milwaukee, Wis., 1996).

S. A. Hagstrom, J. Neitz, M. Neitz, “Ratio of M/L pigment gene expression decreases with retinal eccentricity,” in Colour Vision Deficiencies XIII, C. R. Cavonius, ed. (Kluwer Academic, Dordrecht, The Netherlands, 1997), pp. 59–66.

Cited By

OSA participates in CrossRef's Cited-By Linking service. Citing articles from OSA journals and other participating publishers are listed here.

Alert me when this article is cited.


Figures (8)

Fig. 1
Fig. 1

Illustration showing each step of the pathway a single cone cell travels during the isolation and amplification procedure.

Fig. 2
Fig. 2

(A) Strategy for PCR amplification from single cone cells. L or M cDNA fragments containing exons 3–5, exon 3, and exon 5 were amplified. The number labels of the primers correspond to those in Table 1, where the primer sequences and their specificities are described. (B) Strategy for PCR amplification from retinal patches. L and M cDNA fragments containing a portion of exon 5 were amplified for use in experiments to estimate M/L cone ratio. A two-step process amplified L-specific exon 3 fragments. The L cDNA exon 3–5 PCR product was used in a second round of PCR to amplify L-specific exon 3.

Fig. 3
Fig. 3

(A) Patch of human photoreceptor mosaic obtained from a male eye donor. The image is magnified 2000× under Hoffman contrast optics. Rods are packed tightly, individual cones are transparent in this view and are located in the larger spaces separated by rods. (B) Patch of human photoreceptor beginning to self-dissociate. Planks of rods and cones are seen breaking away and dispersing from the intact mosaic.

Fig. 4
Fig. 4

(A) Typical field of photoreceptor cells. Individual morphologically distinguishable rods (black arrow) and cones (white arrow) are visible. A 10–15 µm micropipette guided under observation is used to collect single cones. (B) Individual cone cell alongside the micropipette. The cell was expelled into a 0.5-ml microcentrifuge tube. The image is taken through the wall of the polypropylene tube and magnified 2000× under Hoffman contrast optics to verify single-cell isolation.

Fig. 5
Fig. 5

PhosphorImage analysis of the ratio of M:L cDNA’s in the retina of four individuals. Amplified cDNA containing exon 5 was digested with RsaI. It is apparent with the unaided eye that each individual is expressing more L cDNA than M cDNA. Both cut (CC) and uncut (UC) controls are labeled.

Fig. 6
Fig. 6

PhosphorImage analysis of five single cones from one individual. Amplified cDNA containing exon 5 from the X-linked pigment genes was digested with RsaI. Each lane represents the analysis of one cone cell. Three cones expressed an L pigment gene, and two cones expressed an M pigment gene.

Fig. 7
Fig. 7

A 35-base-pair region of exon 5 sequence from two different single cone cells from one individual. One cell contains a cDNA sequence identical to that of an L gene, and the other contains a cDNA sequence identical to that of an M gene. Nucleotide differences that distinguish an L cone from an M cone are labeled.

Fig. 8
Fig. 8

PhosphorImage analysis of five single L cones from donor 54. Amplified L cDNA containing exon 3 was digested with BstYI targeting the nucleotide polymorphism at position 1026. Each lane represents a single cone cell. Two different subtypes of L genes are shown to be expressed. Three of the cone cells express the cut L gene fragment, and the other two cells express the uncut L gene fragment.

Tables (6)

Tables Icon

Table 1 Primers Used in the PCR

Tables Icon

Table 2 PCR Thermal Cycling Parameters

Tables Icon

Table 3 Comparison of the Proportion of M to L mRNA and M to L Cones

Tables Icon

Table 4 Single-Cone-Cell Analysis for Four Male Eye Donors

Tables Icon

Table 5 PhosphorImage Analysis of Single Cone Cells Digested with RsaI

Tables Icon

Table 6 PhosphorImage Analysis of Single L Cone Cells Digested with Bst YI

Metrics