Abstract
Abstract: :
Purpose: Despite their descriptive name, a very small population of cones survives in the retinas of coneless transgenic mice. We sought to determine if this small number of receptors can support vision. Methods: For all tests comparable measurements were made on coneless mice and on normal littermates. ERGs were recorded from corneal electrodes. A flicker photometric procedure was used to measure spectral sensitivity. A variety of adaptation and test conditions were employed to elicit signals from different receptor types. Cones were labeled using opsin antibodies and PNA. Behavioral measurements of visual sensitivity were made in a three–alternative, forced–choice discrimination task. Results: Cones of the normal mouse contain either or both M and UV photopigments. In support of earlier results (Soucy et al., Neuron, 1998, 21, 481–493), we found that only a small population of cones (<5% of the normal total) survive in the coneless mouse and that these survivors typically contain only UV pigment and are most prevalent in the ventral part of the retina. ERGs measured in coneless mice under photopic test conditions (light adaptation, 12.5 Hz flicker) show no reliable responses to middle and long wavelength test lights, but small and highly reliable signals can be recorded to UV test lights. V–log I functions were obtained for coneless and normal mice using a UV test light and with accessory light adaptation sufficient to eliminate any signals stemming from rods or M cone pigment. ERG amplitudes at saturation were about ten times smaller in coneless than in normal mice. Spectral sensitivity measurements verify that these signals arise from the mouse UV cone pigment. The visual sensitivities of coneless and normal mice are being assessed in behavioral tests. Increment thresholds measured on scotopic backgrounds (0.045 cd/m2) are not reliably different for 4–5 month old coneless and normal mice. Conclusions:Despite their almost complete lack of cones, reliable cone–based signals can be recorded in coneless mice. These reflect contributions from a very small number of surviving cones containing viable UV photopigment. The results have implications for the use of such animals in research and, more generally, for understanding the retention of visual function following severe loss of photoreceptors.
Keywords: transgenics/knock–outs • opsins • electroretinography: non–clinical