Blue Sight Improvement in Aging Eyes Red Light Dose

https://www.researchgate.net/publication/342531647_Optically_improved_mitochondrial_function_redeems_aged_human_visual_decline

670 nm, 40 mW/cm^2

7.2 J/cm^2

illuminate dominant eye every morning 3 minutes daily 2 weeks

22% improvement tritan system

Use 670 nm light to improve photoreceptor performance

Rod and cone performance declined significantly at approximate age 40

no impact on younger

40 or over sig improvements in

color contrast sensitivity for the blue visual xis (tritan) known to display mitochondrial vulnerability

red improved, not significantly

 

Optically improved mitochondrial function redeems aged human visual decline

Article (PDF Available)inThe Journals of Gerontology Series A Biological Sciences and Medical Sciences · June 2020 with 691 Reads

DOI: 10.1093/gerona/glaa155

Cite this publication

Abstract
The age spectrum of human populations is shifting towards the elderly with larger proportions suffering physical decline. Mitochondria influence the pace of ageing as the energy they provide for cellular function in the form of adenosine triphosphate (ATP) declines with age. Mitochondrial density is greatest in photoreceptors, particularly cones that have high energy demands and mediate colour vision. Hence, the retina ages faster than other organs, with a 70% ATP reduction over life and a significant decline in photoreceptor function.
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Optically improved mitochondrial function redeems aged human visual decline
Harpreet Shinhmar, MSc1, Manjot Grewal, BSc1, Sobha Sivaprasad, MBBS, PhD1,
Chris Hogg1, Victor Chong, MBBS, PhD2, Magella Neveu, PhD1 and Glen Jeffery,
D.Phil1
1Institute of Ophthalmology, University College London and 2Boehringer Ingelheim
Running Heading: Improving aged colour perception
Correspondence to:
Glen Jeffery
Institute of Ophthalmology 11-43 Bath St
University College London
London EC1V 9EL, UK
g.jeffery@ucl.ac.uk
Main text word count: 2487
Number of data elements: 1
Page 1 of 15 Journal of Gerontology: Biological Sciences
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Abstract
The age spectrum of human populations is shifting towards the elderly with larger
proportions suffering physical decline. Mitochondria influence the pace of ageing as the
energy they provide for cellular function in the form of adenosine triphosphate (ATP)
declines with age. Mitochondrial density is greatest in photoreceptors, particularly cones that
have high energy demands and mediate colour vision. Hence, the retina ages faster than other
organs, with a 70% ATP reduction over life and a significant decline in photoreceptor
function.
Mitochondria have specific light absorbance characteristics influencing their performance.
Longer wavelengths spanning 650->1000nm improve mitochondrial complex activity,
membrane potential and ATP production. Here we use 670nm light to improve photoreceptor
performance and measure this psychophysically in those aged 28 to 72 years. Rod and cone
performance declined significantly after approximately 40 years of age. 670nm light had no
impact in younger individuals, but in those around 40 years and over, significant
improvements were obtained in colour contrast sensitivity for the blue visual axis (tritan)
known to display mitochondrial vulnerability. The red visual axis (protan) improved but not
significantly. Rod thresholds also improved significantly in those >40 years. Using specific
wavelengths to enhance mitochondrial performance will be significant in moderating the
ageing process in this metabolically demanding tissue.
Key words: Ageing, Photobiomodulation, Colour vision
Page 2 of 15Journal of Gerontology: Biological Sciences
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Human ageing is a major societal problem and the retina ages faster than other organs, partly
due to its high metabolic rate (1,2). Here 30% of central rods die and cones have reduced
function by 70 years of age (3–5). The pace of ageing is partly controlled by the cells
metabolism regulated by its mitochondria that produce ATP to fuel cell function. When
mitochondria decline, they have reduced membrane potential and ATP synthesis. When this
occurs, mitochondria can increase production of reactive oxygen species that increases
systemic inflammation and can signal cell death (6).
Mitochondrial density is greatest in photoreceptors and their decline can be linked to
reductions in retinal function and the onset of age related disease (7). However, aged
mitochondrial performance can be improved optically because mitochondria absorb longer
wavelengths, including those beyond the limits of human vision and this is often termed
photobiomodulation. Light induced improvements in mitochondrial function are associated
with an increase in mitochondrial membrane potential and ATP production (8,9). Further,
long wavelength light can improve retinal and general central nervous system function that
has declined due to age or mitochondrial insult (10–12). It has also been shown that
photobiomodulation can improve aged murine retinal function (13). However, the mouse
retina lacks a peak in cone density centrally and ages very differently from primates (14).
Further, rodents commonly avoid light and do not use vision as their primary sensory
modality.
Here we use longer wavelengths to determine if this treatment can improve aged human
retinal function. Specifically we test the hypothesis that relatively brief daily exposures to
670n
Methods
Twenty four healthy subjects of both sexes were used with University College London ethical
approval. They ranged from 28-72 years. The cut-off point between younger and older groups
was >38 years, with age as the only significant variable. Different subjects were used to
measure rod (scotopic) thresholds and colour contrast sensitivity (CCS), which were
undertaken at different times. There were 12 individuals in each group. In the CCS group
there were 6 younger (5 female and 1 male) and 6 older (4 female and 2 male) subjects, and
in the scotopic threshold group there were 6 younger (4 females and 2 males) and 6 older (4
female and 2 males) subjects. 670nm light devices were based on simple commercial DC
torches with ten 670nm LEDs mounted behind a light diffuser embedded in a tube that was
4cm in diameter. Energies at the cornea were approximately 40mW/cm-2 which often resulted
in a mild green after image for approximately 5-10 seconds. Participants were asked to use
the light to illuminate their dominant eye every morning for 3 minutes and to repeat this daily
for 2 weeks. These metrics were selected because they fell within the range used in a large
number of animal experiments. 670nm illumination was largely confined to the central retina
comprising the peaks in rod and cone density.
Cone function. CCS was assessed by measuring colour contrast thresholds across the protan
(red visual axis) and tritan (blue visual axis) axes using a computer graphics system,
‘Chromatest’, on 12 healthy subjects of progressive ages with no known ocular or systemic
diseases (Mean age, 43.1 years; Range, 28-68 years; Standard deviation = 13.7). For CCS
measurements, subjects were seated at a fixed distance from the stimulus monitor such that
the optotype letters subtended a 1.3 degree angle on the retina. The letters were displayed on
a randomised noise background to ensure stimulus equiluminance. They appeared either in
red or blue to test protan and tritan axes respectively. The software utilises binary search
algorithm to determine thresholds. Three baseline recordings were taken prior to onset of
Page 4 of 15Journal of Gerontology: Biological Sciences
5
670nm exposure and after. Final CCS recordings were taken on the last day of treatment.
Results were analysed from initial baseline recordings and final recordings taken after 670nm
exposure. Test re-test variability was 0.5% for protan thresholds and 1.4% for tritan
thresholds.
Rod function. Rod thresholds were also determined before and after 670nm exposure in 12
healthy subjects that were different from the CCS group. 670nm application times were as
above (Mean age, 47.8 years; Range, 29-72 years; Standard deviation = 16.5). Subjects had
their pupils dilated to maximize photon capture and were dark adapted for 40 minutes.
Retinal sensitivities were measured with the Medmont dark-adapted chromatic perimeter
(Medmont, Australia) with a stimulus size of 1.73° (Goldmann size V) using 3 decibel (dB)
steps (6-3 staircase threshold strategy). Light stimuli (505-nm presented for 200 ms) were
presented at 17 test points distributed within the central 24° of the retina at 4°, 6°, 8° and 12°
eccentricity to the fovea. Appropriate lens correction was used for a viewing distance of 30
cm. Subjects were instructed to fixate on a central target and were monitored during testing
using an in-built infrared camera. Because measurements were in dB, higher values represent
improved detection. Test re-test variability was within 1.5dB.
Statistical Analysis. Data were graphed and analysed using GraphPad Prism 6 (GraphPad,
San Diego, CA) with a Wilcoxon matched-pairs signed rank test for significance.
Measurements comparing younger and older groups were analysed with a Mann-Whitney U
test for significance.
Page 5 of 15 Journal of Gerontology: Biological Sciences
6
Results
In each of the 3 visual functions examined at baseline there were signs of decline from
approximately 40 years of age. However, this needs qualification as data presented are not
displayed with age as a linear variable. In the tritan axis, baseline colour contrast sensitivity
increased significantly over about 40 years compared to younger subjects by maximum of
47% and an average of around 20% (Figure 1A, p 0.0001).
Over the total group spanning 28-68 years of age there was a significant improvement in
tritan thresholds after exposure to 670nm by 14% (p 0.01) represented by lower values.
However, when the total group was divided into younger and older, the improved thresholds
were clearly the result of positive shifts in those over the age of 38 where there was a 22%
improvement (p 0.001), while younger individuals showed no change (Figure 1B, p >
0.05). Hence, 670nm treatment in older subjects improved tritan thresholds bringing them
towards levels found in younger individuals. However, significant differences remained
between the younger baseline and older treated (p 0.01). Protan thresholds showed no
change after 670nm exposure in the younger group (Figure 1C, p > 0.05), but it did improve
by approximately 10% in the older subjects, although this did not reach statistical
significance (Figure 1D, p > 0.05).
Scotopic thresholds were measured in decibels (dB) where improved sensitivity results in
increased numerical values. Improved sensitivity was found in 8 of the 12 subjects, 3 of
which were under the age of 40 (Figure 1E). But there was no statistically significant changes
in the younger group (p > 0.05). However, in line with the group tested for tritan thresholds,
older individuals showed significant improvement (Figure 1F, p 0.05). While significant
improvements in photoreceptors function were found for both rods and cones, subjects did
not report any subjective changes in their vision.
Page 6 of 15Journal of Gerontology: Biological Sciences
7
Discussion
We show improved aged human photoreceptor function following relatively brief exposure to
670nm light that modulates mitochondria, but there were differences between protan and
tritan thresholds reflecting different features specific to the two cone colour systems. The
tritan system improved by approximately 22% in older subjects. The tritan axis is partly
based on short wavelength sensitive cone function. These cells are relatively frail and suffer
disproportionality in age and disease including diabetes (15). Further, we have recently
shown in old world primates that S-cones contain fewer mitochondria than other cone classes
and are more reliant on glycolysis for ATP production of ATP. This may increase their pace
of ageing (16). In explaining the relative increased magnitude of improvement in tritan
function over protan, it is possible that there is a smaller margin of error in S-cone
mitochondrial function due to their reduced number. Hence, 670nm may have greater impact
on them. However, the protan system also improved by around 10% in older subjects even
though this was not statistically significant.
A potential factor influencing tritan sensitivity is the progressive yellowing of the human lens
with age, which will absorb shorter wavelengths and theoretically has the potential to impact
our measurements (17). However, it is now known that there is compensation for these
changes with mechanisms that stabilize colour appearance independent of changes in the lens
(18). Although, there is no evidence that there are significant changes in lens opacity between
35–40 years that could explain the differences in baseline between our younger and older
groups. Also, changes in lens opacity would not undermine the value of the results obtained
following 670nm exposure over baseline.
The ability to improve cone function is of importance because these cells, unlike rods, do not
die with age in primates including humans (3). This includes blue cones that share molecular
Page 7 of 15 Journal of Gerontology: Biological Sciences

 

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