Topography of the long- to middle-wavelength sensitive cone ratio in the human retina assessed with a wide-field color multifocal electroretinogram

Abstract

The topographical distribution of relative sensitivity to red and green lights across the retina was assayed using a custom-made wide-field color multifocal electroretinogram apparatus. There were increases in the relative sensitivity to red compared to green light in the periphery that correlate with observed increases in the relative amount of long (L) compared to middle (M) wavelength sensitive opsin mRNA. These results provide electrophysiological evidence that there is a dramatic increase in the ratio of L to M cones in the far periphery of the human retina. The central to far peripheral homogeneity in cone proportions has implications for understanding the developmental mechanisms that determine the identity of a cone as L or M and for understanding the circuitry for color vision in the peripheral retina.

Fig. 1

The mf-ERG hardware, example mf-ERG response profile, and analysis of concentric rings representing different retinal eccentricities. (a) The stimulator was designed and constructed out of specially shaped circuit boards so that when placed edge-to-edge created a geodesic dome. Super bright LEDs were then aimed to a focal point and cyclic summation was used to extract topographical regions. The 650 nm LEDs were on in the photograph. (b) A typical mf-ERG response profile obtained from the device. (c) To compare different retinal eccentricities, ERG amplitudes were averaged from “rings” of increasing eccentricity. Analysis was complicated by the fact that the nose and upper brow obstructed the light entering the eye to a variable extent in different subjects. Unreliable data between trials and subjects were commonly found in these areas. To maintain reliability of collected data, only areas labeled in red, orange, and green were used in the ring averages.

Fig. 2

Intensity response functions obtained with the mf-ERG. Each panel represents 6 conditions. The light colored symbols represent responses to the 527 nm LED and the darker symbols represent responses from the 650 nm LED. Different symbols represent different eccentricities; diamonds, ring 2; filled circles, ring 3; triangles, ring 4. Dichromats were used as controls and served to calibrate the system. (a) Average results for four deuteranopes. (b) Results for a protanope. Theoretical estimates of sensitivity to the red and green LED wavelengths are in close agreement with measured sensitivity differences for both deuteranopes and protanopes. (c, d) Subjects JG and JK with low foveal cone ratios showed significant increases in sensitivity to red light as a function of eccentricity. (e, f) Subjects MM and MP had higher foveal cone ratio and showed little to no increase in sensitivity to red light as a function of eccentricity.

Fig. 3

L and M cone contributions to flicker ERG obtained using conventional ERG flicker photometry verses those obtained using the wide-field mf-ERG. Different symbols represent different eccentricities; diamonds, ring 2; filled circles, ring 3; triangles, ring 4. Foveal cone ratios estimated from conventional flicker photometric ERGs correlate well with inner rings from mf-ERG, however, in the far periphery all subjects approach 100% contribution from L cones.