Fenofibrate may prevent ocular surface squamous metaplasia

Normally used to lower triglyceride levels in the blood, fenofibrate may have some potential as a preventative agent to prevent ocular surface squamous metaplasia.

Dry Eyes

Individuals with severe dry eyes are at higher risk of developing ocular surface squamous metaplasia.

The ocular surface of the eyes are composed of a mucous membrane consisting of non-keratinized epithelium. However, in a pathologic process called squamous metaplasia, the epithelium become keratinized. This usually happens in patients with severe deficiencies in the tear film and has been linked to chronic inflammation. At present, available treatments for dry eyes, such as artificial tears or amniotic membrane patching do not satisfactorily manage squamous metaplasia.

Peroxisome proliferator-activated receptors (PPARs) are a type of nuclear hormone receptors for transcription factors and are expressed in tissues in which fatty acid oxidation is present. It has been shown previously that PPAR-γ may inhibit the expression of pro-inflammatory cytokines such as metalloproteinases, TNF-α, IL-6, and IL-β. In this pre-clinical study using a mouse model, the effect of the PPAR-α agonist fenofibrate on ocular surface squamous metaplasia induced by benzalkonium chloride (BAC). BAC is typically used as a preservative in ophthalmic drops.

Squamous metaplasia was induced after 16 days of topical ophthalmic BAC. There were four treatment groups: (1) BAC and no treatment; (2) BAC and a vehicle; (3) BAC and fenofibrate; (4) and BAC, fenofibrate, and intraperitoneal MK886, which is a PPAR antagonist. The tear film was evaluated in the mice, and histopathologic examination of mouse eyes was undertaken.

Results showed that fenofibrate suppressed the formation of an unstable tear film in the mice treated with BAC. In addition, in these mice, cytokeratin 10 and Ki67 were also lower than in other groups. Cytokeratin 10 is an intermediate filament specific to epidermal keratinocytes, while Ki67 is a marker for proliferation. The number of goblet cells were also maintained in mice treated with fenofibrate, as well as the number of F4/80-positive cells and TNF-α and IL-6 mRNA levels. Goblet cells are responsible for synthesizing and secreting the mucous components of the tear film. F4/80 is a marker of classically active macrophages, while TNF-α and IL-6 are inflammatory cytokines. Results also showed that these effects of fenofibrate can be decreased by the inhibitor MK886.

In conclusion, fenofibrate has been shown to affect the mechanisms leading to ocular surface squamous metaplasia in this pre-clinical model. Fenofibrate therefore has some potential as a preventative agent in patients at risk for developing ocular surface squamous metaplasia, such as in those with severe dry eye disease.

He, H., Liang, M., Li, L., Luo, S., Fang, X., & He, H. et al. (2020). PPAR-α Agonist Fenofibrate Suppressed the Formation of Ocular Surface Squamous Metaplasia Induced by Topical Benzalkonium Chloride. Investigative Ophthalmology & Visual Science, 61(3), 54. doi: 10.1167/iovs.61.3.54

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