Melanopsin-Dependent Persistence and Photopotentiation of Murine Pupillary Light Responses

Abstract

Unique photoreceptive properties of intrinsically photosensitive RGCs confer resistance to bleaching and/or adaptation under continuous bright illumination to the pupillary light response and suggest the presence of a photopigment with multiple absorption states.

Expected and Unexpected Properties of Melanopsin Signaling

“…Mawad and Van Gelder's conclusions from their failure to find photopotentiation in ipRGCs recorded in vitro are primarily discordant with those of previous in vitro studies using heterologous expression of melanopsin (Melyan et al, 2005;Panda et al, 2005;Koyanagi et al, 2005) rather than with previous in vivo results. A previous study from the Seattle group (Zhu et al, 2007) is in agreement with ours (Mure et al, 2007) in concluding that light can, under appropriate conditions, enhance (or photopotentiate) pupil constriction and that this response is melanopsin dependent (although they disagree as to its basis in melanopsin bistablity, suggesting instead a downstream effect). In our view, the most parsimonious explanation, which can account for the broadest range of relevant results, although requiring further confirmation, is simply that melanopsin bistability has functional consequences both in vitro and in vivo.…”

“…Mawad and Van Gelder propose several possible explanations for this discrepancy, including interactions of rod and cone inputs with melanopsin intrinsically photosensitive retinal ganglion cell (ipRGC) physiology, differences related to developmental factors (postnatal versus adult), and differences between their in vitro conditions and local in vivo environment. They also suggest that our observed augmentation due to long wavelength light occurs downstream of the retinal ipRGC action potential, as suggested in their previous study (Zhu et al, 2007). We suggest that another possible source of the discrepant findings could be the use of short wavelength (480 nm) test and reference lights of 10 14 photons/cm 2 /sec by Mawad and Van Gelder, which was previously shown to cause saturation of the response in both neonatal and adult retinas (Tu et al, 2005).…”

Restoration of visual function in retinal degeneration mice by ectopic expression of melanopsin

“…We performed several tests of visual function. The first was the PLR (25)(26)(27). A high-threshold PLR is retained in rd/rd mice, mediated by the small complement of native melanopsin cells (4,26).…”

Melanopsin-dependent light avoidance in neonatal mice

“…Figure 3B shows the mixture of NBQX, AP5, AP4, and DHβE (middle trace) (11,30) effectively blocks the short latency photoreceptordriven responses in RGCs recorded from a P16 WT mouse (top trace). This same mixture of synaptic blockers failed to block the light-driven ipRGC responses in a P8 WT mouse (Fig.…”