Organization of the human trichromatic cone mosaic

Abstract

Using high-resolution adaptive-optics imaging combined with retinal densitometry, we characterized the arrangement of short- (S), middle- (M), and long- (L) wavelength-sensitive cones in eight human foveal mosaics. As suggested by previous studies, we found males with normal color vision that varied in the ratio of L to M cones (from 1.1:1 to 16.5:1). We also found a protan carrier with an even more extreme L:M ratio (0.37:1). All subjects had nearly identical S-cone densities, indicating independence of the developmental mechanism that governs the relative numerosity of L/M and S cones. L:M cone ratio estimates were correlated highly with those obtained in the same eyes using the flicker photometric electroretinogram (ERG), although the comparison indicates that the signal from each M cone makes a larger contribution to the ERG than each L cone. Although all subjects had highly disordered arrangements of L and M cones, three subjects showed evidence for departures from a strictly random rule for assigning the L and M cone photopigments. In two retinas, these departures corresponded to local clumping of cones of like type. In a third retina, the L:M cone ratio differed significantly at two retinal locations on opposite sides of the fovea. These results suggest that the assignment of L and M pigment, although highly irregular, is not a completely random process. Surprisingly, in the protan carrier, in which X-chromosome inactivation would favor L- or M-cone clumping, there was no evidence of clumping, perhaps as a result of cone migration during foveal development.

Figure 1.

Identification of S cones in the cone mosaic. a, Averaged retinal images after a full bleach of L- and M-cone pigment, after dark adaptation, and calculated absorptance images. S cones are identified as a sparse array of dim cones in the absorptance image. b, Histogram of individual cone full absorptance values. S cones are identifiable as a low-absorptance peak.

Figure 2.

Scatter plot of cone absorptance after 650 nm bleach versus after 470 nm bleach. L and M cones comprise two distinct distributions. L cones are represented by the lower distribution, because they absorb relatively less after the 650 nm bleach and relatively more after the 470 nm bleach than M cones. S cones have been excluded from this plot.

Figure 3.

Examples of absorptance angle histograms used to identify L and M cones. The best-fitting L- and M-cone Gaussians and their sum are superimposed on each histogram. The vertical dashed line marks the intersection of the L and M curves; cones falling to the left of this line are identified as L, and cones falling to the right are identified as M.

Figure 4.

False color images showing the arrangement of L (red), M (green), and S (blue) cones in the retinas of different human subjects. All images are shown to the same scale.

Figure 5.

Examples of cumulative histogram comparison plots for hypothetical clumped (top) and regularly distributed (bottom) S-cone submosaics. The solid line is the fraction of inter-S-cone separations within a particular distance value for each mosaic versus that for the average of 100 simulated mosaics with random S-cone placement. The dashed lines represent the maximum and minimum bounds of the random simulations. If the solid line were to lie entirely between the two dashed lines, then the arrangement of the S cones in the hypothetical mosaics would be indistinguishable from random. The clumped mosaic shows significantly more short inter-S-cone separations than expected for a random mosaic, whereas the regularly distributed mosaic exhibits significantly fewer short inter-S-cone separations than the random expectation.

Figure 6.

Cumulative histogram comparison plots for the S-cone submosaic. The solid line is the fraction of inter-S-cone separations within a particular distance value for the actual mosaic versus that for the average of 100 random simulations. The dashed lines represent the maximum and minimum bounds of the random simulations. If the solid line lies entirely between the two dashed lines, then the arrangement of the S-cone submosaic is indistinguishable from random.

Figure 7.

Comparison of adaptive optics- and ERG-derived estimates of L:M cone ratio. Eight subjects were from this study (filled circles), and two subjects were from the study by Roorda and Williams (1999) (open triangles). ERG data for these two subjects were published previously (Brainard et al., 2000). Shown on the abscissa is a histogram of ERG-derived L:M ratios for 62 color-normal males (Carroll et al., 2002) (including JC, BS, and RS from the current study). The solid line is the best-fitting linear regression for the eight subjects in the current study (r ² = 0.98). Inclusion of the Brainard et al. (2000) data only slightly diminishes the correlation (r ² = 0.95). Error bars represent SD.

Figure 8.

Examples of cumulative histogram comparison plots for hypothetical mosaics with clumped (top) and regularly distributed (bottom) L and M cones. The solid line is the fraction of inter-M-cone separations within a particular distance value for each mosaic versus that for the average of 100 simulated mosaics with random cone placement. The dashed lines represent the maximum and minimum bounds of the random simulations. If the solid line were to lie entirely between the two dashed lines, then the arrangement of the M cones in the hypothetical mosaics would be indistinguishable from random. The clumped mosaic shows significantly more short inter-M-cone separations than expected for a random mosaic, whereas the regularly distributed mosaic exhibits significantly fewer short inter-M-cone separations than the random expectation.

Figure 9.

Cumulative histogram comparison plots for the M-cone submosaic (L-cone submosaic for HS). The solid line is the fraction of intercone separations within a particular distance value for the actual mosaic versus that for the average of 100 random simulations. The dashed lines represent the maximum and minimum bounds of the random simulations. If the solid line lies entirely between the two dashed, lines then L- and M-cone arrangement is indistinguishable from random.