Lacrimal Hypofunction as a New Mechanism of Dry Eye in Visual Display Terminal Users

BACKGROUND: Dry eye has shown a marked increase due to visual display terminal (VDT) use. It remains unclear whether reduced blinking while focusing can have a direct deleterious impact on the lacrimal gland function. To address this issue that potentially affects the life quality, we conducted a large-scale epidemiological study of VDT users and an animal study. METHODOLOGY/PRINCIPAL FINDINGS: Cross sectional survey carried out in Japan. A total of 1025 office workers who use VDT were enrolled. The association between VDT work duration and changes in tear film status, precorneal tear stability, lipid layer status and tear secretion were analyzed. For the animal model study, the rat VDT user model, placing rats onto a balance swing in combination with exposure to an evaporative environment was used to analyze lacrimal gland function. There was no positive relationship between VDT working duration and change in tear film stability and lipid layer status. The odds ratio for decrease in Schirmer score, index of tear secretion, were significantly increased with VDT working year (P = 0.012) and time (P = 0.005). The rat VDT user model, showed chronic reduction of tear secretion and was accompanied by an impairment of the lacrimal gland function and morphology. This dysfunction was recovered when rats were moved to resting conditions without the swing. CONCLUSIONS/SIGNIFICANCE: These data suggest that lacrimal gland hypofunction is associated with VDT use and may be a critical mechanism for VDT-associated dry eye. We believe this to be the first mechanistic link to the pathogenesis of dry eye in office workers

マウス胸腺脂肪化時期の検討

The thymus has an important role in the immune reaction. The lymphocytes localized both in thymic cortex and in medulla, known as T cells, proliferate in an environment of the epithelial reticular cells. T cells educated to react against non-self materials enter the circulation and function in peripheral immunity. Thymus of the mouse has almost developed and grown to its natal size by the 18 days gestation. After the birth thymus grows at a somewhat slower rate until puberty. It subsequently shows a decrease both in size and in weight. That is due to the decrease in the lymphocyte-accumulated region and to the partial replacement by fat tissue. The process is so-called age"involution". Fat cells are classified as connective-tissue cells. They must develop and proliferate in the capsule or in the trabecula of the thymus after birth, because no typical fat cells containing lipid droplets are observed at birth.We examined when fat cells appeared in the thymus after the birth. Fat cells are known to express leptin, so that the appearance of leptin mRNA was detected by the PCR method. The expression of leptin was detected as early as in the thymus of the 3 week-old mouse and increased with the age. It is sugested that fat tissue development begins immediately after the birth and precedes to the age involution in the thymus, although that the cortex and medulla develops until puberty

Neurodegenerative influence of oxidative stress in the retina of a murine model of diabetes

Aims/hypothesis: Diabetic retinopathy is a progressive neuro-degenerative disease, but the underlying mechanism is still obscure. Here, we focused on oxidative stress in the retina, and analysed its influence on retinal neurodegeneration, using an antioxidant, lutein. Methods: C57BL/6 mice with streptozotocin-induced diabetes were constantly fed either a lutein-supplemented diet or a control diet from the onset of diabetes, and their metabolic data were recorded. In 1-month-diabetic mice, reactive oxygen species (ROS) in the retina were measured using dihydroethidium and visual function was evaluated by electroretinograms. Levels of activated extracellular signal-regulated kinase (ERK), synaptophysin and brain-derived neurotrophic factor (BDNF) were also measured by immunoblotting in the retina of 1-month-diabetic mice. In the retinal sections of 4-month-diabetic mice, histological changes, cleaved caspase-3 and TUNEL staining were analysed. Results: Lutein did not affect the metabolic status of the diabetic mice, but it prevented ROS generation in the retina and the visual impairment induced by diabetes. ERK activation, the subsequent synaptophysin reduction, and the BDNF depletion in the diabetic retina were all prevented by lutein. Later, in 4-month-diabetic mice, a decrease in the thickness of the inner plexiform and nuclear layers, and ganglion cell number, together with increase in cleaved caspase-3- and TUNEL-positive cells, were avoided in the retina of lutein-fed mice. Conclusions/interpretation: The results indicated that local oxidative stress that has a neurodegenerative influence in the diabetic retina is prevented by constant intake of a lutein-supplemented diet. The antioxidant, lutein may be a potential therapeutic approach to protect visual function in diabetes

Oral Administration of Royal Jelly Restores Tear Secretion Capacity in Rat Blink-Suppressed Dry Eye Model by Modulating Lacrimal Gland Function

<div><p>Tears are secreted from the lacrimal gland (LG), a dysfunction in which induces dry eye, resulting in ocular discomfort and visual impairment. Honey bee products are used as a nutritional source in daily life and medicine; however, little is known about their effects on dry eye. The aim of the present study was to investigate the effects of honey bee products on tear secretion capacity in dry eye. We selected raw honey, propolis, royal jelly (RJ), pollen, or larva from commercially available honey bee products. Tear secretion capacity was evaluated following the oral administration of each honey bee product in a rat blink-suppressed dry eye model. Changes in tear secretion, LG ATP content, and LG mitochondrial levels were measured. RJ restored the tear secretion capacity and decrease in LG ATP content and mitochondrial levels to the largest extent. Royal jelly can be used as a preventative intervention for dry eye by managing tear secretion capacity in the LG.</p></div

Effect of royal jelly on lacrimal gland function.

<p>A: ATP levels. B: Mitochondria content (Left). Imaging of the mitochondrial membrane potential (Right). Scale bar, 20 µm. (n = 12–18 LG) C: AMPK activity in a normal lacrimal gland after the oral administration of RJ (n = 6 LG). All data represent the mean ± SD. * <i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001, versus the vehicle (ATP and mitochondria) or initial (AMPK).</p

Royal jelly restored tear secretion in a rat blink-suppressed dry eye model.

<p>A: Changes in body weight. B: Changes in tear secretion (Left). (n = 10 rats) Representative photographs of tear secretion patterns measured by a cotton thread (Right). The arrow shows the wetted length by tear secretion. C: Effect of RJ on corneal surface damage. Changes in the grading score (lower, n = 9 rats), Typical pattern of staining (Upper). Punctate staining appeared in the whole area of cornea surface with the vehicle treatment. D: Histopathological changes in the LG. HE staining (Left upper). VAMP8 immunostaining (Left lower). Scale bar, 20 µm (HE) or 50 µm (VAMP8). Acinar cell size (Right, n = 6 LG). All data represent the mean ± SD. **<i>P</i><0.01, ***<i>P</i><0.001 versus the vehicle.</p

Effect of royal jelly on lacrimal gland acinar [Ca²⁺]i mobilization.

<p>A: Changes in [Ca²⁺]i in normal lacrimal acinar cells. Pseudo colored images of [Ca²⁺]i (Upper). Scale bar, 50 µm. The bar graph shows the summarized data of the amplitudes of [Ca²⁺]i responses. (n = 13 acini) B: Effect of 10-HDE (Left, n = 14 acini). The typical response to 10HDE (Right). C: Effect of AG1478 (n = 10 acini). D: Effect of muscarinic acetylcholine pathway inhibitors (Left, n = 22–53 acini). Responses to the stimulation with or without inhibitors (Right). The arrow indicates the time at which RJ or CCH was applied to the cells. Dotted line over the trace indicated the presence of each inhibitor. Relative responses were calculated as a percentage of the decrease in the RJ-induced [Ca²⁺]i response with the application of an inhibitor relative to the stimulation seen with RJ alone in each acinus. All data represent the mean ± SE. ***P<0.001 versus RJ (Fig 4C) or without an inhibitor (Fig 4D).</p

Evaluation of various honey bee products.

<p>A: Effect of various honey bee products on tear secretion in a rat blink-suppressed dry eye model. The oral administration doses of honey, pollen, larva, propolis, and RJ were 1200, 200, 200, 200, and 300 mg/kg, respectively (n = 5 rats). B: Protein secretion rate from normal LG after stimulation by various honey bee products. The LG was stimulated with 500 µg/ml of each honey bee product (n = 5 LG). All data represent the mean ± SD. *<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001 versus the vehicle.</p