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Alan Rupp, Tiffany Schmidt, Kylie Chew, Benjamin Yungher, Kevin Park, Samer Hattar; ipRGCs mediate ipsilateral pupil constriction. Invest. Ophthalmol. Vis. Sci. 2013;54(15):310.
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For decades, the retina was believed to be the only photosensitive tissue in mammals. Recently, however, Xue et al. reported that the isolated iris muscle is photosensitive in a variety of mammalian species and directly constricts in response to extremely bright light due to expression of the photopigment melanopsin in iris muscle cells (Xue et al., Nature 2011). In agreement, Xue et al. also identified enhanced ipsilateral pupil constriction relative to contralateral constriction, but with greater sensitivity than in isolated iris. These findings are at odds with previous reports that melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are the sole conduit through which light mediates the pupillary light reflex (PLR) via a projection to the olivary pretectal nucleus (OPN) (Guler et al., Nature 2008). Therefore, we sought to investigate a potential role for ipRGCs in the enhanced ipsilateral PLR at physiological light intensities.
To characterize the PLR of mice with various retinal perturbations, we stimulated mice with ambient room light, sunlight, or bright blue light and measured the ipsilateral and contralateral pupil constriction. Pupil constriction was quantified by comparing the pupil area in darkness by the area in light. To determine ipRGC projections, we stained tissue in mice expressing alkaline phosphatase in ipRGCs only.
Here we report that physiological levels of light fail to drive pupil constriction in the absence of neuronal transmission or in animals lacking RGCs. These results argue against direct constriction of the pupil by melanopsin-expressing iris muscle cells at these light intensities. Furthermore, we were surprised to find that axonal fibers originating from melanopsin-expressing cells in the retina are observed near the iris muscle and in the cornea. Consistent with ipRGCs driving the iris muscle constriction independent of inputs from the brain, we show that ipsilateral but not contralateral constriction of the pupil muscle persists in animals that retain only the 200 ipRGCs thought to mediate circadian photoentrainment (Chen et al., Nature 2011).
These results strongly suggest that the direct PLR at physiological light intensities is driven by input from ipRGCs that project to the iris, and is not an intrinsic property of the iris muscle.
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