We have examined the effects of the age on the pupil response to high intensity (300
) long (660
nm, red) or short (470
nm, blue) wavelength light.
Pupil responses to red light did not correlate to age. As both the baseline pupil size and the lens transmission of blue light decreases with age, a reduction in pupil response to blue light might be expected. We found a significantly enhanced response for sustained and early poststimulus pupil contraction at high intensity blue light stimulus condition.
For the maximal pupil contraction and the late poststimulus response at either red or blue high intensity light conditions, the effect of age was non-significant with a small numerical increase. The lack of a correlation between age and the maximal pupil contraction amplitude suggests that the outer photoreceptors (rods and cones) input to the neural signal of the ipRGCs to the pupil light reflex is relatively resistant to change due to the aging process. For the late poststimulus pupil response (assessed as the sum of amplitudes (area under the curve, AUC) within 10 to 30
s after light offset), a possible reason for the lack of correlation to age could be increasing contribution of supranuclear influences on the pupil size which results in fluctuating pupil size during the late phase of re-dilatation and, thus, greater variability [35
In contrast, advancing age did positively correlate with increasing magnitude of the sustained pupil contraction during continuous light stimulation, as well as the early post-illumination pupil response (poststimulus AUC within 0 to 10 seconds after light offset), but this relationship was specific to the short wavelength light stimulus condition.
The enhanced response (sustained and early poststimulus contraction) to high intensity blue light was found, despite the known decrease in lens transmission (in our study found to be 1% per year) and adjustment of outcome results for the baseline pupil. If age was substituted by the in vivo measured lens transmission of blue light in the correlation analysis, the pupil response change to blue light was only found significant for the early poststimulus AUC at high intensity stimulus conditions. The lower correlation between the pupil response and the lens transmission, as opposed to age, indicates that the effect of transmission cannot, by itself, account of the effect of age on the early poststimulus AUC, presumably a marker of the melanopsin-mediated ipRGC activity.
The finding that the pupil maintains a contracted state during and after continuous blue light stimulation of high intensity is not unique to our study and, in fact, has been demonstrated to be the signature feature of melanopsin activation [6
The novel finding of our study is that these physiological markers of melanopsin-mediated ipRGC activity become more robust with increasing age. This is rather an unexpected finding, given that certain physiologic changes in the eye that occur with age, such as yellowing of the lens and attrition of retinal ganglion cells [38
], might intuitively be expected to cause decreased pupil responses to blue light with increasing age.
This suggests that there exist other age related factors that might work to enhance the melanopsin-mediated pupil responses. One of the factors could be the light scatter of the lens which is known to increase with age in parallel to the decrease in lens transmission [39
]. The scatter leads to a changed distribution of light over the retina, and one might speculate, if this could increase activation of the unevenly distributed melanopsin containing ipRCGs.
Could it be that ipRGCs undergo some age related adaptive processes in order to keep their functioning at an optimal level? Some evidence exists that structural changes appear in rod outer segments, i.e., they increase with age giving a greater functional capacity, while the number of rods decreases with age [42
There is also some data on age-related changes that occur in the suprachiasmatic nucleus (SCN) in terms of unchanged neuron number with increasing age, which might lend support to the notion that the optic pretectal nucleus (OPN) (the nucleus which integrates the various afferent signals driving the pupil light reflex) might undergo similar changes as well [43
The additional finding of a log linear increase in pupil response with increasing light intensity has been demonstrated previously in experimental studies [4
] and, in this study, did not show any threshold effect within the intensity range of 3 to 300
Our example where we compared pupil responses of a 30
year old subject to a 60
year old subject supports the adaptation hypothesis: a gradual and great decrease in blue light transmission with years resulted in enhanced pupil responses (sustained and early poststimulus contraction) to bright blue light by appr.10–20%, whereas a decrease in light intensity by 2 log units (from 300 to 3
) during the experimental procedure led to a linear decrease in these pupil responses to blue light by 30–50% independently of age.
It is beyond the scope of this study to understand where in the pupil light reflex pathway that this augmentation of pupil response to blue light seen in older healthy subjects occurs. Additional studies are needed to clarify which other mechanisms are maybe responsible for enhancement of these ipRGC mediated pupil responses occurring with age.