title: Intrinsically photosensitive retinal ganglion cell function in relation to age: a pupillometric study in humans with special reference to the age-related optic properties of the lens.
abstract: BACKGROUND
  The activity of melanopsin containing intrinsically photosensitive ganglion retinal cells (ipRGC) can be assessed by a means of pupil responses to bright blue (appr.480 nm) light. Due to age related factors in the eye, particularly, structural changes of the lens, less light reaches retina. The aim of this study was to examine how age and in vivo measured lens transmission of blue light might affect pupil light responses, in particular, mediated by the ipRGC.
  
  
  METHODS
  Consensual pupil responses were explored in 44 healthy subjects aged between 26 and 68 years. A pupil response was recorded to a continuous 20 s light stimulus of 660 nm (red) or 470 nm (blue) both at 300 cd/m2 intensity (14.9 and 14.8 log photons/cm2/s, respectively). Additional recordings were performed using four 470 nm stimulus intensities of 3, 30, 100 and 300 cd/m2. The baseline pupil size was measured in darkness and results were adjusted for the baseline pupil and gender. The main outcome parameters were maximal and sustained pupil contraction amplitudes and the postillumination response assessed as area under the curve (AUC) over two time-windows: early (0-10 s after light termination) and late (10-30 s after light termination). Lens transmission was measured with an ocular fluorometer.
  
  
  RESULTS
  The sustained pupil contraction and the early poststimulus AUC correlated positively with age (p=0.02, p=0.0014, respectively) for the blue light stimulus condition only.The maximal pupil contraction amplitude did not correlate to age either for bright blue or red light stimulus conditions.Lens transmission decreased linearly with age (p<0.0001). The pupil response was stable or increased with decreasing transmission, though only significantly for the early poststimulus AUC to 300 cd/m2 light (p=0.02).
  
  
  CONCLUSIONS
  Age did not reduce, but rather enhance pupil responses mediated by ipRGC. The age related decrease of blue light transmission led to similar results, however, the effect of age was greater on these pupil responses than that of the lens transmission. Thus there must be other age related factors such as lens scatter and/or adaptive processes influencing the ipRGC mediated pupil response enhancement observed with advancing age.
authors.affiliation: Department of Ophthalmology, Glostrup Hospital, Ndr. Ringvej 57, 2600 Glostrup, Copenhagen, Denmark.
authors.forename: Kristina
authors.initials: K
authors.lastname: Herbst
authors.forename: Birgit
authors.initials: B
authors.lastname: Sander
authors.forename: Henrik
authors.initials: H
authors.lastname: Lund-Andersen
authors.forename: Adam Elias
authors.initials: AE
authors.lastname: Broendsted
authors.forename: Line
authors.initials: L
authors.lastname: Kessel
authors.forename: Michael Stormly
authors.initials: MS
authors.lastname: Hansen
authors.forename: Aki
authors.initials: A
authors.lastname: Kawasaki
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000502:physiology*; D019540:Area Under Curve; D005260:Female; D006801:Humans; D007908:Lens, Crystalline / Q000502:physiology*; D008027:Light; D008297:Male; D008875:Middle Aged; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism; D011680:Pupil / Q000502:physiology*; D012025:Reflex, Pupillary / Q000528:radiation effects*; D012165:Retinal Ganglion Cells / Q000378:metabolism; D017299:Rod Opsins / Q000378:metabolism; D000099210:Melanopsin
chemical_list: D017299:Rod Opsins; D000099210:Melanopsin