A comparison of the electroretinogram in the cone-dominant thirteen-lined ground squirrel and the rod-dominant Brown Norway rat

Abstract

Purpose : Rodents have been used extensively as models of ocular disease owing to their small size, low cost of maintenance and ease of genetic manipulation. Unfortunately, the retinae of the most commonly utilized species – mice and rats – are rod-dominant and poorly recapitulate both the anatomy and function of the human central retina. By contrast, the retina of the thirteen-lined ground squirrel (13-LGS) is highly cone-rich, making it an attractive potential model for studying diseases that primarily affect cone structure and function in humans. Herein we use electroretinography (ERG) to assess the visual function of the diurnal 13-LGS in comparison to that of the nocturnal rod-dominant Brown Norway (BN) rat.

Methods : Five-month old 13-LGS (n=6) and BN rats (n=6) initially underwent dark- (-4 to 1 log cd.s/m²) and light-adapted (0 to 1 log cd.s/m²) single flash (1Hz, 4ms) and flicker (5, 15 and 30Hz) ERG recordings to assess baseline retinal function of each species. The relative contributions of ON- and OFF-bipolar cells to the 13-LGS and BN rat ERG were assessed using a light-adapted, long-duration (500ms) flash stimulus following intravitreal injection of glutamatergic (2mM APB) and kainate (10μM ACET) receptor agonists.

Results : Dark-adapted a- and b-wave amplitudes were higher in the BN rat model compared to the 13-LGS under low light conditions (-4 to -1 log cd.s/m²), reflecting the relatively greater proportion of rod photoreceptors. The a- and b-wave amplitudes were greater in the 13-LGS at higher intensity light stimuli under both dark-adapted (0.48 to 1 log cd.s/m²) and light-adapted (0 to 1 cd.s/m², 25 cd/m² background) conditions, reflecting the greater contribution of cones to the overall ERG response. Intravitreal injection of 2mM APB and 10μM ACET significantly decreased b-wave and d-wave response (by paired-t test), respectively, in both the BN rat and 13-LGS models, indicating post-synaptic signaling pathways are similar in both species.

Conclusions : ERG responses for both BN rats and 13-LGS reflected the relative proportions of cone photoreceptors present within the retinae. That the 13-LGS is highly cone-dominant may make it a useful model for studying human central retinal function.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.