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      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


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          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.


          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/m 2 intensity (14.9 and 14.8 log photons/cm 2/s, respectively). Additional recordings were performed using four 470 nm stimulus intensities of 3, 30, 100 and 300 cd/m 2. 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.


          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/m 2 light ( p = 0.02).


          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.

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          Most cited references30

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          Melanopsin-expressing ganglion cells in primate retina signal colour and irradiance and project to the LGN.

          Human vision starts with the activation of rod photoreceptors in dim light and short (S)-, medium (M)-, and long (L)- wavelength-sensitive cone photoreceptors in daylight. Recently a parallel, non-rod, non-cone photoreceptive pathway, arising from a population of retinal ganglion cells, was discovered in nocturnal rodents. These ganglion cells express the putative photopigment melanopsin and by signalling gross changes in light intensity serve the subconscious, 'non-image-forming' functions of circadian photoentrainment and pupil constriction. Here we show an anatomically distinct population of 'giant', melanopsin-expressing ganglion cells in the primate retina that, in addition to being intrinsically photosensitive, are strongly activated by rods and cones, and display a rare, S-Off, (L + M)-On type of colour-opponent receptive field. The intrinsic, rod and (L + M) cone-derived light responses combine in these giant cells to signal irradiance over the full dynamic range of human vision. In accordance with cone-based colour opponency, the giant cells project to the lateral geniculate nucleus, the thalamic relay to primary visual cortex. Thus, in the diurnal trichromatic primate, 'non-image-forming' and conventional 'image-forming' retinal pathways are merged, and the melanopsin-based signal might contribute to conscious visual perception.
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            High sensitivity of the human circadian melatonin rhythm to resetting by short wavelength light.

            The endogenous circadian oscillator in mammals, situated in the suprachiasmatic nuclei, receives environmental photic input from specialized subsets of photoreceptive retinal ganglion cells. The human circadian pacemaker is exquisitely sensitive to ocular light exposure, even in some people who are otherwise totally blind. The magnitude of the resetting response to white light depends on the timing, intensity, duration, number and pattern of exposures. We report here that the circadian resetting response in humans, as measured by the pineal melatonin rhythm, is also wavelength dependent. Exposure to 6.5 h of monochromatic light at 460 nm induces a two-fold greater circadian phase delay than 6.5 h of 555 nm monochromatic light of equal photon density. Similarly, 460 nm monochromatic light causes twice the amount of melatonin suppression compared to 555 nm monochromatic light, and is dependent on the duration of exposure in addition to wavelength. These studies demonstrate that the peak of sensitivity of the human circadian pacemaker to light is blue-shifted relative to the three-cone visual photopic system, the sensitivity of which peaks at approximately 555 nm. Thus photopic lux, the standard unit of illuminance, is inappropriate when quantifying the photic drive required to reset the human circadian pacemaker.
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              Factors affecting light-adapted pupil size in normal human subjects.

              To investigate the effect of age, gender, refractive error, and iris color on light-adapted pupil size in humans. Pupil diameters of 91 subjects (age range, 17 to 83 years) with normal, healthy eyes were measured using an objective infrared-based continuous recording technique. Five photopic ocular illuminance levels were used (2.15 to 1050 lumens m-2), and the accommodative status of each subject was precisely controlled at a constant level. Pupil size decreased linearly as a function of age at all illuminance levels. Even at the highest illuminance level, there was still a significant effect of age upon pupil size. The rate of change of pupil diameter with age decreased from 0.043 mm per year at the lowest illuminance level to 0.015 mm per year at the highest. In addition, the variability between pupil sizes of subjects of the same age decreased by a factor of approximately two as luminance was increased over the range investigated. Pupil size was found to be independent of gender, refractive error, or iris color (P > 0.1). Of the factors investigated, only chronologic age had a significant effect on the size of the pupil. The phenomenon of senile miosis is present over a wide range of ocular illuminance levels.

                Author and article information

                BMC Ophthalmol
                BMC Ophthalmol
                BMC Ophthalmology
                BioMed Central
                3 April 2012
                : 12
                : 4
                [1 ]Department of Ophthalmology, Glostrup Hospital, Ndr. Ringvej 57, 2600, Glostrup, Copenhagen, Denmark
                [2 ]Department of Neuro-ophthalmology, Hôpital Ophtalmique Jules Gonin, Avenue de France 15, Lausanne, 1004, Switzerland
                [3 ]Department of Clinical Sciences Ophthalmology, University of Umea, S90185, Umea, Sweden
                Copyright ©2012 Herbst et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                : 17 August 2011
                : 3 April 2012
                Research Article

                Ophthalmology & Optometry
                Ophthalmology & Optometry


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