Abstract
Purpose :
The pupillary light reflex (PLR) originates in the retina, in the intrinsically photosensitive retinal ganglion cells (ipRGCs) whose function is driven by intrinsic inputs (melanopsin) as well as extrinsic rod and cone inputs. We recently reported that in the dark-adapted mouse, rod inputs to ipRGCs support the PLR across scotopic, mesopic, and photopic light intensities, whereas melanopsin contributes only at photopic light intensity and cones contribute little (Beier et al. 2022 Cell Rep. 39, 111003). The goal of this study is to start investigating the respective contributions of the different inputs to ipRGCs to the PLR under light-adapted conditions.
Methods :
Unanesthetized mice were restrained for up to 30 min by headposts that were placed using a minimally invasive surgical technique we developed that does not necessitate drilling through the skull. One eye was dilated and exposed to a series of 30-s light stimuli ranging from 0.01 Lux to 1,000 Lux, while consensual PLR was recorded in the other eye using a NeurOptics A-2000 pupillometer. We used pan connexin-36 knockout (pan-Cx36 KO) animals, in which the primary and secondary rod ON pathways are absent, and C57BL6/J wildtype (WT) animals as controls. Light intensity is expressed as log (lux), the PLR threshold as the light intensity to elicit 5% constriction, and I50 as the intensity to elicit 50% constriction.
Results :
In dark-adapted WT mice (n=3), the PLR threshold was -1.22 +/- 0.308 (mean +/- sem), and I50 was 0.038 +/- 0.046, which agrees well with previous studies. Following 15 min of light-adaptation (50 lx), the intensity response function was shifted to the right by 1.5 log units (I50 = 1.37 +/- 0.26, p=0.00745). Both dark-adapted and light-adapted intensity response functions were shifted to the right in the pan-Cx36 KO mice (n=3) (I50 = 1.52 +/- 0.23 [dark-adapted] and 1.51 +/- 0.26 [light-adapted], p=0.969).
Conclusions :
Light adaptation of the PLR in the WT animals shifts the PLR intensity response function to the same position as in the mutants in which the primary and secondary rod ON pathways are absent. Our findings therefore suggest that the contributions of the primary and/or secondary rod pathways are reduced following light adaptation. Ongoing experiments will further dissect the respective contributions of rods, cones, and/or melanopsin in driving the PLR under light adaptation.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.