Corneal diffusion and metabolism of 12(R)-hydroxyeicosatetraenoic acid (12(R)HETE)

Area of Science:

• Ocular pharmacology
• Lipid metabolism
• Corneal physiology

Background:

• 12(R)-hydroxyeicosatetraenoic acid (12(R)HETE) is an eicosanoid with potential roles in ocular inflammation.
• Understanding its corneal transport and metabolism is crucial for assessing its ocular effects.

Purpose of the Study:

• To quantify the corneal diffusion and metabolism of tritiated 12(R)HETE in an in vitro rabbit cornea model.
• To determine if 12(R)HETE or its metabolites can reach the corneal endothelium.

Main Methods:

• Tritiated 12(R)HETE was applied to the tear side of in vitro-mounted rabbit corneas under varying conditions (intact, epithelium removed, or both removed).
• Radioactivity was measured in corneal layers and perfusates using scintillation spectroscopy.
• High-performance liquid chromatography (HPLC) analyzed 12(R)HETE and metabolite concentrations.

Main Results:

• The intact cornea rapidly metabolized 12(R)HETE into more polar compounds, including 8(R)-hydroxyhexadecatrienoic acid (8(R)HHDTrE).
• Both 12(R)HETE and 8(R)HHDTrE diffused through the stroma to the endothelium.
• Epithelium removal reduced metabolism but allowed stromal diffusion; removal of both layers showed minimal metabolism.

Conclusions:

• 12(R)HETE and its metabolites can diffuse from the corneal epithelium through the stroma.
• These compounds may potentially exert adverse effects on the corneal endothelium.