Abstract
We investigated the effect of a peroxisome proliferator-activated receptor α (PPARα) agonist after corneal alkali injury. Fenofibrate 0.05% (PPARα agonist group) or vehicle (Vehicle group) was topically instilled onto the rat cornea after injury. Histological, immunohistochemical, and real-time reverse transcription PCR analyses were performed. PPARα-positive cells were observed among basal cells of the corneal epithelium in normal and alkali-burned corneas. The number of infiltrating neutrophils and macrophages at the corneal limbus was lower in the PPARα agonist group. Interleukin-1β (IL-1β), IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor-An mRNA expression was suppressed in the PPARα agonist group compared to the Vehicle group. mRNA levels of nuclear factor kappa B (NF-κB) in corneal tissue were not different. However, NF-κB was expressed in the cytoplasm of basal cells in the PPARα agonist group and in the nucleus in the Vehicle group. MCP-1 was more weakly expressed in the PPARα agonist group. The PPARα agonist inhibited inflammation during the early phase after injury. Anti-inflammatory effects of the PPARα agonist included prevention of up-regulation of proinflammatory cytokines and MCP-1, and prevention of inflammatory cell infiltration into the injured cornea. Thus, a PPARα agonist may be a promising treatment for corneal injury.
Highlights
For good vision, transparency of the cornea is essential
In theInnormal rat cornea, peroxisome proliferator-activated receptor α (PPARα), β, and γ-positive cells were observed among the epithelial the normal rat cornea, PPARα, β, and γ-positive cells were observed among the epithelial basement cells
PPARα, β, and γ-positive cells were observed in the epithelial basement cells of normal cornea. (A–C; A: PPARα stain, B: PPARβ stain, C: PPARγ stain)
Summary
Injuries that damage the corneal stroma often result in scarring. Since inflammation and angiogenesis are deeply involved in scar tissue formation, agents that can suppress these phenomena have long been sought. One of the new suppression candidates is peroxisome proliferator-activated receptors (PPARs). PPAR is a nuclear receptor that belongs to the steroid hormone receptor superfamily. Three isoforms of PPARs, which vary in their tissue distribution, have been confirmed and include PPARα, β, and γ [1,2,3]
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