Mechanism for Altered Dark-Adapted Electroretinogram Responses in DBA/2J Mice Includes Pupil Dilation Deficits

Abstract

Purpose The DBA/2J (D2) mouse is an established model of pigmentary glaucoma, a type of primary open angle glaucoma. Prior studies have documented defects in flash electroretinogram (ERG) responses in D2 mice, but the origin of those defects is not clear. The purpose of this study was to understand the origin of these A-wave and B-wave changes in D2 ERGs. Materials and Methods To accomplish this, we analyzed the differences between 9-month-old DBA/2J-Gpnmb+ (D2-control) and D2 mouse eyes in relation to ERG responses, intraocular pressure (IOP), outer nuclear layer thickness, and pupil area. Results D2 scotopic ERGs showed lower A-wave amplitude and longer implicit time as well as a significant rightward shift in the intensity-response curve. D2 IOP increased at approximately seven months of age and had a weak correlation with the ERG A-wave sensitivity. Outer nuclear layer thickness was not significantly different in D2s compared to D2-control retinas. D2 mouse pupils also showed abnormal pupillary shape and no dilation following treatment with tropicamide eye drops. The pupil size moderately correlated with the A-wave sensitivity and this was pharmacologically replicated in C57Bl/6J mice following administration of pilocarpine to constrict the pupils. However, pilocarpine treatment did not affect ERG amplitudes. Conclusions These data suggest that the smaller pupil sizes prevented light from reaching the photoreceptors and thus contributed to reduced ERG sensitivity in D2 mice. The reduced ERG A-wave amplitude in D2 mice likely results from dysfunctional photoreceptor responses.