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

CONSORT flowchart.

<p>CONSORT flowchart.</p

Clinical Evaluation of a Royal Jelly Supplementation for the Restoration of Dry Eye: A Prospective Randomized Double Blind Placebo Controlled Study and an Experimental Mouse Model

<div><p>Background</p><p>Dry eye is a multifactorial disease characterized by ocular discomfort and visual impairment. Lacrimal gland function has been shown to decrease with aging, a known potent risk factor for dry eye. We have previously found that orally administrated royal jelly (RJ) restored tear secretion in a rat model of dry eye.</p><p>Methods and Findings</p><p>We examined the effects of RJ oral administration on dry eye in this prospective, randomized, double-blind, placebo-controlled study. Forty-three Japanese patients aged 20–60 years with subjective dry eye symptoms were randomized to an RJ group (1200 mg/tablet, six tablets daily) or a placebo group for 8 weeks. Keratoconjunctival epithelial damage, tear film break-up time, tear secretion volume, meibum grade, biochemical data, and subjective dry eye symptoms based on a questionnaire were investigated at baseline, and at 4 and 8 weeks after intervention. Adverse events were reported via medical interviews. In the RJ group, tear volume significantly increased after intervention (<i>p</i> = 0.0009). In particular, patients with a baseline Schirmer value of ≤10 mm showed a significant increase compared with baseline volume (<i>p</i> = 0.0005) and volume in the placebo group (<i>p</i> = 0.0051). No adverse events were reported. We also investigated the effect of RJ (300 mg/kg per day) administration using a mouse model of dry eye. Orally repeated administration of RJ preserved tear secretion, potentially through direct activation of the secretory function of the lacrimal glands.</p><p>Conclusion</p><p>Our results suggest that RJ improves tear volume in patients with dry eye.</p><p>Trial Registration</p><p>Registered NO. the University Hospital Medical Information Network in Japan (UMIN000014446)</p></div

Effects of royal jelly (RJ) on dry eye symptoms assessed by ophthalmological examinations.

<p>Effects of royal jelly (RJ) on dry eye symptoms assessed by ophthalmological examinations.</p

Baseline characteristics of patients with dry eye who received placebo (PB) or royal jelly (RJ).

<p>Baseline characteristics of patients with dry eye who received placebo (PB) or royal jelly (RJ).</p

Change in Schirmer values in patients with dry eye symptoms who received royal jelly (RJ) or placebo (PB) tablets.

<p>Error bars represent standard deviation. **<i>p</i><0.01 vs. pre-treatment values.</p