Journal Name:
Arch. Ophthalmol.
Article Title:
Topical Omega-3 and Omega-6 Fatty Acids for Treatment of Dry Eye.
Date Written:
2008
Volume:
126
Number:
2
Page:
219
Author(s):
Rashid, S.; Jin, Y.; Ecoiffier, T.; Barabino, S.; Schaumberg, D.A.; Dana, M.R.
Article:
Dry eye syndrome (DES) is a highly prevalent health problem that affects more than 10 million people, primarily women, in the United States. It is a frequent cause of problems with sustained visual activities such as reading and driving. Inflammation has been recognized as an important component of DES.
Naturally occurring essential polyunsaturated fatty acids (PUFA) of omega-3 (n-3) and omega-6 (n-6) series are promising natural anti-inflammatory agents shown to have beneficial effects in many inflammatory conditions such as rheumatoid arthritis and ulcerative colitis. Recent studies have shown beneficial effects of dietary supplementation of FAs in DES. Several important issues remain unresolved, in particular whether FAs can be provided topically, thereby bypassing excess caloric intake and gastrointestinal adverse effects associated with their oral supplementation. The purpose of this study was to evaluate the efficacy of topical n-3 and n-6 FAs using the controlled environmental chamber murine model of dry eye.
Formulations containing alpha linolenic acid (ALA), linoleic acid (LA), combined ALA and LA, or vehicle alone, were applied to dry eyes induced in mice. Corneal fluorescein staining and the number and maturation of corneal CD11b cells were determined by a masked observer in the different treatment groups. Real-time polymerase chain reaction was used to quantify expression of inflammatory cytokines in the cornea and conjunctiva.
Dry eye induction significantly increased corneal fluorescein staining; CD11b cell number and major histocompatibility complex Class II expression; corneal IL-1alpha and tumor necrosis factor alpha (TNF-a) expression; and conjunctival IL-1a, TNF-a, interferon a, IL-2, IL-6, and IL-10 expression. Treatment with ALA significantly decreased corneal fluorescein staining compared with both vehicle and untreated controls. Additionally, ALA treatment was associated with a significant decrease in CD11b cell number, expression of corneal IL-1a and TNF-a, and conjunctival TNF-a.
The ALA-treated eyes showed a significant reversal in corneal epithelial damage, manifested by decreased fluorescein staining as compared with the untreated eyes and eyes treated with vehicle, LA, or combined ALA and LA. The exact mechanism of corneal epithelial repair in the ALA-treated eyes is unknown but could theoretically be mediated directly by ALA or its metabolites, EPA and DHA. At the molecular level, dry eye induction leads to a persistent increase in corneal expression of IL-1a and TNF-a. These cytokines are important mediators of inflammation implicated in the pathogenesis of corneal ulceration, uveitis, and corneal transplant rejection.
Of the formulations tested, only the ALA treatment was effective in decreasing the corneal and conjunctival expression of IL-1a and TNF-a. Because these cytokines are released early in response to epithelial cell damage and are also released by activated macrophages, the epithelial repair and decreased macrophages infiltration in the ALA-treated cornea may account for the decreased cytokine expression. Dietary ALA has been shown to decrease endotoxin-induced macrophage production of TNF-a.
Topical ALA treatment led to a significant decrease in dry eye signs and inflammatory changes at both cellular and molecular levels. Topical application of ALA may be a novel therapy to treat the clinical signs and inflammatory changes accompanying dry eye syndrome. The use of ALA to treat dry eye and potentially other inflammatory ocular surface conditions, would allow more flexibility in dosing. Further studies are indicated to optimize dosing and formulations that are maximally effective.
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