Rod and Cone Coupling Modulates Photopic ERG Responses in the Mouse Retina

Yichao Li; Ethan D Cohen; Haohua Qian

doi:10.3389/fncel.2020.566712

Rod and Cone Coupling Modulates Photopic ERG Responses in the Mouse Retina

Front Cell Neurosci. 2020 Sep 25:14:566712. doi: 10.3389/fncel.2020.566712. eCollection 2020.

Authors

Yichao Li¹, Ethan D Cohen², Haohua Qian¹

Affiliations

¹ Visual Function Core, National Eye Institute (NEI), National Institutes of Health, Bethesda, MD, United States.
² Division of Biomedical Physics, Office of Science and Engineering Labs, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, MD, United States.

Abstract

Light adaptation changes both the sensitivity and maximum amplitude (R_max) of the mouse photopic electroretinogram (ERG) b-wave. Using the ERG, we examined how modulation of gap junctional coupling between rod and cones alters the light-adapted ERG. To measure changes, a b-wave light adaptation enhancement factor (LAEF), was defined as the ratio of R_max after 15 min light adaptation to R_max recorded at the onset of an adapting light. For wild-type mice (WT), the LAEF averaged 2.64 ± 0.29, however, it was significantly reduced (1.06 ± 0.04) for connexin 36 knock out (Cx36KO) mice, which lack electrical coupling between photoreceptors. Wild type mice intraocularly injected with meclofenamic acid (MFA), a gap junction blocker, also showed a significantly reduced LAEF. Degeneration of rod photoreceptors significantly alters the effects of light adaptation on the photopic ERG response. Rd10 mice at P21, with large portions of their rod photoreceptors present in the retina, exhibited a similar b-wave enhancement as wildtype controls, with a LAEF of 2.55 ± 0.19. However, by P31 with most of their rod photoreceptors degenerated, rd10 mice had a much reduced b-wave enhancement during light-adaptation (LAEF of 1.54 ± 0.12). Flicker ERG responses showed a higher temporal amplitude in mesopic conditions for WT than those of Cx36KO mice, suggesting rod-cone coupling help high-frequency signals to pass from rods to cone pathways in the retina. In conclusion, our study provides a novel method to noninvasively measure the dynamics and modulation by the light adaptation for rod-cone gap junctional coupling in intact eyes.

Keywords: gap-junction; light-adaptation; mouse; photopic ERG; photoreceptor; rd10; retinal degeneration; rod-cone interaction.