ORIGINAL ARTICLE

Prevention of scattered light-induced asthenopia and fatigue by apolarized filter
Keiichi Hiramoto1, Yurika Yamate1, Kumi Orita1, Mika Jikumaru1, Emiko Kasahara1, Eisuke F. Sato1, Shinzo
Tamura2 & Masayasu Inoue1
1
Department of Biochemistry and Molecular Pathology, Osaka City University Medical School, Osaka, Japan, and 2Polalens Institute,TALEX Optical Co., Osaka, Japan

Summary
Key words:
cortisol; fatigue; polarized glass; scatteredlight; TGF-b

Correspondence:
Keiichi Hiramoto, Department of Biochemistry andMolecular Pathology, Osaka City University Medical
School, 1-4-3 Asahimachi, Abeno, Osaka 5458585, Japan.
Tel: 181 6 6645 3722
Fax: 181 6 6645 3721
e-mail: hiramoto@msic.med.osaka-cu.ac.jp

Accepted for publication:
11 January 2010

Conflicts of interest:
None declared.

E

Background: It has been well documented that a long-time irradiation of the eye by a strong
light elicits eyestrain and fatigue. To elucidate the mechanism for the induction of light-induced
fatigue and asthenopia, changes in the mouse were analyzed after white light-irradiation tothe eye.
Methods: C57BL/6j male mice were irradiated with white light in a specially designed room
equipped with four mirrors covering all areas of its four walls to elicit diffused reflected
light, and changes in their plasma levels of cortisol, INF-g, interleukin-10 (IL-10) andtransforming growth factor-b (TGF-b) were analyzed.
Results: Irradiation of mice with scattered white light significantly decreased the motional
activity of animals, suggesting the occurrence of fatigue. Biochemical analysis and enzymeimmunoassay revealed that the irradiation of mice significantly elevated the plasma levels ofcortisol, IFN-g, IL-10 and TGF-b. All these changes were not observed with mice irradiatedwith the light in a similar room not equipped with mirrors. These changes were successfully
inhibited by a polarized glass filter but not by a non-polarized filter with a similar
absorbance.
Coclusions: These observations suggest that irradiation of the eye by scattered reflected lightstimulated a stress response via hypothalamo-pituitary-adrenal axis to enhance the secretionof cortisol from the adrenal grand and increase the plasma levels of cytokines.

xposure of the skin and eye to strong sunlight has been
known to elicit fatigue and immunosuppression either byactivating the proopiomelanocortin (POMC) pathway in dermal
keratinocytes and/or by stimulating the POMC-dependent
hypothalamo-pituitary-adrenal (HPA) axis, a major pathway forstress response (1–3). Ultraviolet lights (UV-A and B) have beenshown to suppress various functions of antigen-presenting
Langerhans cells in the skin and inhibit the sequence of
immunological reactions at the site of irradiation (4–6). As UV
irradiation causes fatigue and immunosuppression, use of asunscreen and/or a sunglass that eliminates UV has been
recommended for the protection of the skin and the preventionof fatigue, particularly in an area exposed to strong sunlight.
Although exposure of the eye to a strong visible light has been
known also to elicit eyestrain, its mechanism and an effective way
to suppress fatigue and asthenopia remain unknown. The present
work describes that irradiation of the eye with scattered reflectionof white light elevated the plasma levels of cortisol, interferon-g(IFN-g), interleukin-10 (IL-10) and transforming growth factorb (TGF-b) and suppressed the motional activity of mice by amechanism that could be inhibited specifically by a polarized
glass filter.

Materials and methods
Animal experiments
Specific pathogen-free and 8-week-old C57BL/6j male mice
(SLC, Hamamatsu, Japan) were subjected to experiments
according to the animal care regulations of the Osaka City
University Medical School. The mice were placed in a scatteredreflection room (Hiramoto model, USO-800, Hiramoto, Osaka,Japan) equipped with a white light at its ceiling (Fig. 1). Theupper half of the side walls were covered with mirrors to reflect
lights effectively and the lower half of the walls were painted withblack color to absorb and eliminate light. The upper and lower
compartments of the room could be separated either by an
ordinary glass (TM-1) or by a specially polarized TOPCON TM1 glass filter (TALEX, Osaka, Japan); the two glasses show similarr 2010 John Wiley & Sons A/S  Photodermatology, Photoimmunology & Photomedicine 26, 89–92

89Hiramoto et al.

Fig. 1. Special device (Hiramoto model USO-800) to irradiate animals
with scattered reflection light.

Fig. 3. Effects of irradiation by scattered reflection light and a polarized
filter on the behavior and plasma components relating to stress andfatigue of animals. Before and 20 min after irradiation of the eye withwhite light in a specially designed room, the motional activity of animals
was determined as described in the text. Irradiation was carried out in thepresence or absence of either TM-1 or TOPCON TM-1 filter. Values aremean  SD derived from six animals. P o 0.05 compared with no-filterirradiation mice.

Analysis of animal behavior and plasma hormones
Before and after irradiation of the mice, their behavior wasmonitored for 20 min using a video-camera (DCR-TRV50, Sony,Tokyo, Japan) and analyzed using a software Smart (Panlab,Barcelona, Spain); the total distance of their movement during
10 min was assumed to be their voluntary action. Blood samples
were obtained from the heart 6 h after irradiation, centrifuged at1000  g for 10 min to obtain plasma samples. Plasma levels ofcortisol, IFN-g, IL-10 and TGF-b were analyzed by enzymelinked immunoassay (ELISA) using commercially available ELISA
kits (cortisol, Oxford Biochemical Research, MI, USA; IL-10 andIFN-g, Pierce Biotechnology, IL, USA; TGF-b, Promega, WI,USA) according to the manufacturer’s instructions.

Fig. 2. Transmission spectrum of TM-1 (a) and TOPCON TM-1 (b)filters.

permeability (30%) to white light and intercepts all UV ofo 390 nm (Fig. 2). In addition, the two glasses adopt the middle
point of the three primary colors. The mice were exposed towhite light (400–700 nm; FL20SN-SDL.NU, NU lamps, ToshibaCo., Tokyo, Japan) for 2 h. The irradiation was 15 W/cm2 andthe height of the light source was 30 cm from the mice.
As a result of having performed a similar examination in themouse in which the scattered reflection light was exposed to thewhole body except eyes, the motional activity and the plasma
cytokine levels did not change compared with the control group(non-irradiation). Therefore, it suggested that the influence
provided in our examination depends on the scattered reflection
light that invaded from the eyes.
90

Statistical analysis
All data were expressed as the mean  SD derived from six
animals and analyzed by either Student’s t-test or ANOVA using
a computer software program. Differences were consideredsignificant when P o 0.05.

Results and discussion
Effect of scattered reflection light on animal behavior
To know the effect of irradiation of scattered reflection light on
the motional activity of mice, their behaviors were analyzed
before and after the irradiation. Irradiation of the eye
significantly decreased the motional activity of animals (Fig. 3).
The same dose of irradiation in a similar room without mirrors
on the walls did not affect the behavior of animals. Thus,irradiation of the eye with scattered reflection light inducedr 2010 John Wiley & Sons A/S  Photodermatology, Photoimmunology & Photomedicine 26, 89–92

Prevention of scattered light by a polarized filter

Fig. 4. Effects of irradiation of scattered reflection light and filters on the plasma concentrations of cortisol (a), IFN-g (b), IL-10 (c) and TGF-b (d).
Before and 6 h after irradiation of the eye with scattered reflection light, plasma concentrations of cortisol, IFN-g, IL-10 and TGF-b were determined.
Values are mean  SD derived from six animals. P o 0.05 compared with experiments without filters.

significant fatigue in animals. The decrease in the motional
activity was strongly suppressed by inserting a speciallypolarized TOPCON TM-1 glass filter between the twocompartments in the room (see Fig. 1). In contrast, theinhibitory effect of an ordinary glass filter TM-1 was fairly low.
Effect of the two filters on plasma levels of cortisol
Irradiation of the eye by the scattered reflection light significantly
increased the plasma levels of cortisol (Fig. 4a). The increase inplasma cortisol was inhibited strongly by a TOPCON TM-1 filterand only slightly by a TM-1 filter.
Effect of irradiation and the two filters on plasma levels ofcytokines
Plasma levels of cytokines were also determined by using ELISA
kits before and after irradiation by scattered reflection light.
Irradiation of the eye markedly increased the plasma levels ofIFN-g, IL-10 and TGF-b (Fig. 4b and d). The increase in theplasma levels of all cytokines was suppressed strongly by aTOPCON TM-1 filter but not by an ordinary TM-1 filter.
A mechanism that could be inhibited specifically by apolarized glass filter
The present work clearly shows that irradiation of the eye by
scattered reflection light increased the plasma levels of cortisol,IFN-g, IL-10 and TGF-b and suppressed the motional activity ofanimals. As a result of our observation, the plasma levels ofcytokine and hormone after the scattered reflection lightirradiation on 0.5, 1, 3, 6, 9, 12 and 24 h showed the highest
levels at 6 h (Fig. 5). In addition, the plasma levels of cytokineand cortisol rapidly increased after irradiation. Therefore, it isFig. 5. Effects of irradiation of scattered reflection light on the plasma
concentrations of cortisol (A) and TGF-b (B). At the indicated times after
scattered reflection light irradiation, plasma samples were collected.
Values are mean  SD derived from six animals.

suggested that changes in cytokine and cortisol and the motional
activity are related closely. These observations indicate that
irradiation of the eye by scattered reflection light induced astress response of animals by activating POMC-dependent HPA
axis to increase the secretion of cortisol by the adrenal gland. AsTGF-b is one of the key molecules that elicit fatigue in animals(7–9), the decrease in the motional activity of the irradiatedanimals seems to reflect the occurrence of eyestrain and/orrelated fatigue.
Previous studies in this laboratory (10) reported that
irradiation of the eye with UVB activated a nitric oxidedependent hypothalamo-pituitary POMC pathway, increased theplasma levels of melanocyte-stimulating hormone (MSH) andr 2010 John Wiley & Sons A/S  Photodermatology, Photoimmunology & Photomedicine 26, 89–92

91

Hiramoto et al.

systemically activated functions of MSH-responsive cells. This
stress response also increased the plasma levels of TGF-b andelicited strong fatigue in the irradiated animals.
The present work also showed that irradiation of the eye bydiffused reflection of visible light also evoked stress response as
judged from the increase in plasma cortisol. Thus, the signaling
pathway that stimulates HPA axis might also be activated byirradiation with the diffused reflection light. As cortisol has beenknow to increase the secretion of TGF-b that suppresses theimmunological activity and elicits fatigue in rodents (11), asimilar mechanism seems to underlie the pathogenesis ofeyestrain. Thus, the special device to elicit scattered reflection
light used in the present work permits studies for the mechanismof eyestrain and related fatigue and to establish efficient methods
to suppress them.
As a specially polarized TOPCON TM-1 glass filter effectively
inhibited the elevation of plasma levels of cortisol, IFN-g, IL-10
and TGF-b, this filter might be useful for the prevention of
fatigue and/or immunosuppression elicited by exposure to ascattered reflection light during the summer season and/or areas
exposed to strong sunlight and reflection light from a screen
elicited by the personal computer and television.

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r 2010 John Wiley & Sons A/S  Photodermatology, Photoimmunology & Photomedicine 26, 89–92