Abstract
Purpose :
When presented with a rod saturating background light, photopic ERG flash response amplitudes gradually increase as a function of time. This light-adapted response is disrupted when connexin-36 (Cx36) is knocked out in cone photoreceptors with b-wave amplitudes at a maximal level as soon as the background light is applied (Zhang et al., IOVS 2020;61(6)24). It is unknown if this response is due to eliminating cone-cone gap junctions or rod-cone gap junctions. To answer this question, we investigated the response to rod-specific disruption of Gjd2, the gene that encodes Cx36.
Methods :
Mice of either sex aged 90 to 120 days were entrained to a 12h light/12h dark cycle. Three genotypes of mice were studied: Rho-iCre75; Gjd2fl/fl (rod-Cx36KO); Gjd2fl/fl (Cre-negative control); Rho-iCre75 mice with no floxed allele. Scotopic and photopic ERGs were recorded as described in Zhang et al. (2020) at mid-subjective night following dark adaptation. Optomotor responses were recorded under photopic conditions to assess visual acuity (spatial frequency threshold) and contrast sensitivity.
Results :
There were no significant differences in scotopic ERG a-wave or b-wave amplitudes between rod-Cx36KO mice and controls (Rho-iCre and Gjd2fl/fl mice). The photopic b-wave amplitude of rod-Cx36KO mice was significantly higher than that of both control groups at all light-adaptation times (p<0.01). In contrast to the gradual increase in photopic b-wave amplitude of the control groups as a function of light-adaptation time, in the rod-Cx36KO mice, there was an immediate and constant increase in amplitude with little or no change over time. There was no significant difference in contrast sensitivity nor visual acuity between the groups (p=0.06 and p=0.83, respectively).
Conclusions :
Our results show that mice with rod specific disruption of Cx36 appeared to enter a fully light adapted state immediately after the introduction of background light, which phenocopies the results observed in cone-specific Cx36KO mice. Thus, rod-cone gap junctions, rather than cone-cone gap junctions, regulate the photopic ERG light-adaptive response.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.