March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
Intrinsically Photosensitive Retinal Ganglion Cells (ipRGCs) Can Respond to Many Hours of Constant Illumination
Author Affiliations & Notes
  • Kwoon Y. Wong
    Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan
  • Footnotes
    Commercial Relationships  Kwoon Y. Wong, None
  • Footnotes
    Support  NIH grants R00 EY18863 and P30 EY007003; Research to Prevent Blindness Scientific Career Development Award
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 4342. doi:
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      Kwoon Y. Wong; Intrinsically Photosensitive Retinal Ganglion Cells (ipRGCs) Can Respond to Many Hours of Constant Illumination. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4342.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Every ipRGC generates an intrinsic melanopsin photoresponse as well as a rod/cone-driven light response. Because both response components are remarkably tonic, ipRGCs have been hypothesized to be capable of very prolonged irradiance detection, e.g. throughout the day. Here, I tested this hypothesis.

Methods: : Eyecups were harvested from dark-adapted Long-Evans rats, and a 3mm x 3mm piece was flattened on a multielectrode array (MEA). The preparation was superfused either with normal Ames to permit rod/cone signaling to ipRGCs, or with Ames containing synaptic blockers to isolate the intrinsic response. Following initial superfusion in darkness, full-field 480-nm light was presented from underneath the MEA for 10 hr. In some experiments, this stimulus was a step increase in intensity; in others, the intensity was ramped up over 2.5 hr to simulate sunrise, then held steady for 5 hr, and finally ramped down over 2.5 hr to mimic sunset. At the end of each experiment, a 1-min brilliant light step was presented to identify ipRGCs as the units that responded throughout the 1 min, since all conventional RGCs respond transiently to such a stimulus (Wong et al. 2007 J. Physiol.).

Results: : In the light step experiment, ipRGC firing rates were elevated throughout the 10-hr light at all suprathreshold intensities. In normal Ames, the threshold was 107 photons cm-2 sec-1, matching the rod input threshold of primate ipRGCs (Dacey et al. 2005 Nature). In synaptic block, the melanopsin threshold was 1010 photons cm-2 sec-1, 1 log unit lower than the threshold previously measured using 1-min light (Tu et al. 2005 Neuron). At 1010 photons cm-2 sec-1, intrinsic responses had onset latencies of 3 - 10 min, and peak latencies often exceeded 1 hr. At light off, firing rates typically required ~30 min to fully return to baseline. In the ramp experiment, ipRGC spiking increased gradually during the 2.5-hr "sunrise" simulation, stayed steady during the 5-hr constant intensity, and dropped gradually in the 2.5-hr "sunset" phase.

Conclusions: : Whereas the cone input to ipRGCs evokes transient light responses (Dacey et al. 2005 Nature), the rod input and the intrinsic response can both sustain spiking for at least 10 hr. The ramp experiment showed that ipRGC spike rates can probably track natural irradiance change throughout the day. The melanopsin transduction cascade can integrate photons over at least 1 hr, and prolonged integration can evoke a sustained intrinsic response at intensities only ~3 log units above the rod threshold. Lastly, the novel rat eyecup preparation used here preserves rod photosensitivity in the face of continued light exposure, thus enabling long-term studies of rod signaling under light-adapted conditions.

Keywords: ganglion cells • retina: proximal (bipolar, amacrine, and ganglion cells) • photoreceptors 

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