AC is one of the world's most common ocular surface diseases, and T helper type 2 (Th2) immune responses are crucial to orchestrating inflammatory responses associated with the disease.
The roles of lipid mediators in the onset and progression of AC, however, have not been fully investigated. Furthermore, although omega-3 fatty acids have previously been found to benefit those suffering from asthma or atopic dermatitis, the underlying mechanisms remain unclear.
Pink-eye in white mice
Based on the above findings, researchers at the university conducted a study on mice that had been placed on a diet rich in omega-3 or omega-6.
They put four-week-old female mice on either an omega-3 or omega-6 diet for two months and performed two instances of sensitisation, the first after 30 days and the second after another 14 days.
From the 26th to 29th day, half the mice in each diet group had eye drops containing 2mg of ragweed pollen in 10ml of phosphate-buffered saline (PBS) applied to each eye daily, while the rest had 10ml of PBS alone applied in the same manner.
Subsequently, 24 hours after the final eye drop applications, the researchers assessed the mice’s eyeballs, eyelids, and ocular conjunctival tissue.
The researchers observed that the omega-3 fatty acids "completely suppressed scratching behaviour" around the mice's eyes, an allergic reaction brought on by the itching associated with AC.
Inflammation and suppression
They also found that the diet rich in omega-3 had helped to alleviate symptoms in both the early and late phases of AC without affecting Th2 immune responses — instead, it did so by altering lipid mediator profiles.
Despite total serum Immunoglobulin E (IgE) levels and expression levels of Th2 cytokines and chemokines in the mice's conjunctiva remaining unaltered by omega-3 fatty acids, they wrote that the infiltration of eosinophils (a variety of white blood cells responsible for fighting off multicellular parasites and certain infections) into the conjunctiva was "dramatically suppressed".
In addition, the levels of pro-inflammatory lipid mediators derived from omega-6 — including those with chemo-attractant properties for eosinophils — were significantly lowered in the conjunctivae of mice placed on the diet rich in omega-3.
As such, they hypothesised that the dietary intake of omega-3 fatty acids were at least partially responsible for alleviating a range of AC symptoms by altering the lipid mediator profile.
On the other hand, the mice on the control omega-6 diet had fatty acid-metabolising enzymes convert free arachidonic acid (ARA) released from cell membranes into pro-inflammatory lipid mediators.
The production of these pro-inflammatory lipid mediators were almost completely suppressed in the mice on the omega-3 diet, possibly through the provision of competitive substrates, such as EPA and its downstream metabolites, for the synthetic enzymes of ARA metabolites in the conjunctiva.
'Safe and practical approach'
In conclusion, they wrote: "This study revealed that dietary omega-3 fatty acids alleviate AC in both the early and late phases by suppressing the production of various pro-inflammatory lipid mediators derived from ARA, which are involved in the pathogenesis of AC.
"In general, Th2 immune responses are regarded as the most important drug targets in allergy; however, the preventive and therapeutic effects of dietary omega-3 fatty acids described in this study were not through modulating Th2 immune responses.
"Instead, at least in the present AC model, lipid mediators derived from ARA seem to play a major role in eliciting allergic symptoms. Although the drugs currently on the market for treating AC can inhibit the production of either prostaglandins or leukotrienes, none blocks both pathways.
"Thus, altering the lipid mediator profile with dietary omega-3 fatty acids may be a safe and practical approach for the prevention and therapeutics of AC, especially given that omega-3 fatty acid consumption is currently declining worldwide."
Source: The FASEB Journal
"Dietary omega-3 fatty acids alter the lipid mediator profile and alleviate allergic conjunctivitis without modulating Th2 immune responses"
Authors: Toshiaki Hirakata, et al.