The color blind retina

Human trichromacy relies on three different cone types in the retina; long- (L), middle- (M), and short- (S) wavelength-sensitive. Dichromatic color vision results from the functional loss of one cone class, however one of the central questions has been whether individuals with this form of red-green color-blindness have lost one population of cones or whether they have normal numbers of cones filled with either of two instead of three pigments. Evidence has accumulated favoring the latter view in which the photopigment in one class of cone is replaced but the issue has not been resolved directly. Berendschot et al. (1996) measured optical reflectance spectra of the fovea for normals and dichromats and their analysis favored the replacement model. Psychophysical experiments, based on frequency of seeing curves, have also provided evidence that the packing of foveal cones in dichromats is comparable to that in trichromats. Most recently, in comparing mean contrast gains derived from the electroretinogram (ERG) for dichromats to those of trichromats, Kremers et al. (1999) concluded that complete replacement occurs in dichromacy. Since these studies, our understanding of the molecular genetics of human color vision defects has increased dramatically. The L and M cone photopigments are encoded by genes that reside in a head-to-tail tandem array on the X-chromosome. Due to this arrangement, there is a high propensity for these genes to undergo unequal homologous recombination. This intermixing of the L and M genes has produced a wide array of genetic causes for red-green color vision defects, though mechanistically they can be placed into two main categories. In one category, the gene(s) for a spectral class of pigment are lost, not expressed, or are replaced with a functional gene for a different spectral class. Alternatively, a gene is replaced by another that encodes a non-functional photopigment. In light of this genotypic variability, it seemed plausible that there could be associated phenotypic variability within what has classically been supposed to be a single class of dichromats. Adaptive optics (AO) enables visualization of cone photoreceptors with unprecedented resolution by correcting for the eye’s aberrations. When combined with retinal densitometry, the spectral identity of individual cones can be deduced and pseudocolor images of the trichromatic cone mosaic in the living human eye can be obtained (see “The trichromatic cone mosaic”). Using this same technique to obtain images of the dichromatic cone mosaic in two individuals for whom the genetic cause of dichromacy was known, we confirm that replacement of the photopigment in what normally would have constituted a third class of cone does occur, though surprisingly one of the dichromats showed, in addition to the loss of his M-cone pigment, a patchy loss of normal cones throughout the photoreceptor mosaic (see the figure below). This finding shows that in some eyes, color blindness can arise from the loss of an entire class of cone.