title: Melanopsin-dependent persistence and photopotentiation of murine pupillary light responses.
abstract: OBJECTIVE
  To determine the relative contributions of inner and outer retinal photoreception to the pupillary light response.
  
  
  METHODS
  Wild-type, retinal degenerate (rd/rd), and melanopsin mutant (opn4(-/-)) mice were tested for pupillary light responsiveness by video pupillometry before, during, and after exposure to supersaturating light intensities. Similar lighting protocols were used to probe responses of intrinsically photosensitive retinal ganglion cells (ipRGCs) recorded with multielectrode arrays ex vivo.
  
  
  RESULTS
  Both outer retinal photoreceptors (rods and cones) and inner retinal photoreceptors (intrinsically photosensitive retinal ganglion cells [ipRGCs]) are sufficient to drive the pupillary light response in mice. After supersaturating light exposure, rather than bleaching or adapting, rd/rd mice showed paradoxical potentiation of responses to subsaturating light exposure. opn4(-/-) mice, in contrast, could not sustain pupillary constriction under continuous bright illumination, and showed desensitization after bright-light exposure. Both the intensity of light necessary to induce potentiation and the spectral sensitivity for sustained and potentiated responses differed from that necessary to trigger pupillary constriction, suggesting that photopotentiation is dependent on a pigment-state distinct from that triggering the pupillary light response itself. Multielectrode array recordings of ipRGCs from rd/rd retinas demonstrated persistent cell firing under continuous light exposure but did not show potentiation.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University Medical School, St. Louis, Missouri, USA.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhu
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Tu
authors.forename: Darcy
authors.initials: D
authors.lastname: Denner
authors.forename: Thomas
authors.initials: T
authors.lastname: Shane
authors.forename: Christine M
authors.initials: CM
authors.lastname: Fitzgerald
authors.forename: Russell N
authors.initials: RN
authors.lastname: Van Gelder
mesh_terms: D000818:Animals; D004594:Electrophysiology; D008027:Light; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology*; D011680:Pupil / Q000528:radiation effects*; D012025:Reflex, Pupillary / Q000502:physiology*; D012162:Retinal Degeneration / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000502:physiology*; D017299:Rod Opsins / Q000502:physiology*; D014741:Video Recording; D000099210:Melanopsin
chemical_list: D017299:Rod Opsins; D000099210:Melanopsin