Topical Omega-3 and Omega-6 Fatty Acids for Treatment of Dry Eye

January 1, 2008 Human Health and Nutrition Data 0 Comments

Topical Omega-3 and Omega-6 Fatty Acids for Treatment of Dry Eye

Year: 2008
Authors: Rashid, S. Jin, Y. Ecoiffier, T. Barabino, S. Schaumberg, D.A. Dana, M.R.
Publication Name: Arch. Ophthalmol.
Publication Details: Volume 126; Number 2; Pages 219 – 225.


To study the efficacy of topical application of alpha-linolenic acid (ALA) and linoleic acid (LA) for dry eye treatment. Formulations containing ALA, 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-1alpha, TNF-alpha, interferon gamma, 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. 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 omega-3 fatty acid may be a novel therapy to treat the clinical signs and inflammatory changes accompanying dry eye syndrome. (Author's abstract)                               
Dry eye syndrome (DES) is a highly prevalent health problem that affects more than 10 million people, primarily women. Inflammation has been recognized as an important component of DES. In a cross-sectional study of 32470 women, women with a higher n-3 FA intake were found to have 68% lower prevalence of DES. It is not known whether FAs can be provided topically, and thus 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. The current study demonstrates for the first time a beneficial effect of topical application of the n-3 FA ALA in treating the ocular signs and reversing the inflammatory changes of dry eye at both molecular and cellular levels. The ALA-treated eyes showed a significant reversal in cornea lepithelial 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 cornea lepithelial 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 the inflammatory biomarkers IL-1a and TNF-a.  Only ALA treatment was effective in decreasing the corneal and conjunctival expression of IL-1a and TNF-a.  In addition, the study also showed a nearly 100-fold increased expression of IL-10 in dry eye conjunctiva which was reduced by ALA.  ALA application showed a reduction in the corneal leukocyticin filtration. This may be partly accounted for by the decreased cytokine expression, especially TNF-a.  The present study did not compare the changes seen with topical ALA treatment with other available topical anti-inflammatory agents, such as steroids; and the authors suggest that such direct comparisons may be worthwhile in future studies.
In summary, the study shows the beneficial effect of ALA omega-3 FA topical application in reversing the signs and the underlying inflammatory changes seen in dry eye. The use of these fatty acids in topical formulations to treat dry eye and potentially other inflammatory ocular surface conditions, would allow more flexibility in dosing. Further studies are clearly indicated to optimize dosing and formulations that are maximally effective. (Editor's comments)

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