Eucalyptol inhibits amyloid‐β‐induced barrier dysfunction in glucose‐exposed retinal pigment epithelial cells and diabetic eyes

Abstract

Hyperglycemia elicits tight junction disruption and blood‐retinal barrier breakdown, resulting in diabetes‐associated vison loss. Eucalyptol is a natural compound found in eucalyptus oil with diverse bioactivities. This study evaluated that eucalyptol ameliorated tight junctions and retinal barrier function in glucose/amyloid‐β (Aβ)‐exposed human retinal pigment epithelial (RPE) cells and in db/db mouse eyes. RPE cells were cultured in media containing 33 mM glucose or 5 μM Aβ for 4 days in the presence of 1–20 μM eucalyptol. The in vivo animal study employed db/db mice orally administrated with 10 mg/kg eucalyptol. Nontoxic eucalyptol inhibited the Aβ induction in glucose‐loaded RPE cells and diabetic mouse eyes. Eucalyptol reversed the induction of tight junction‐associated proteins of ZO‐1, occludin‐1 and matrix metalloproteinases in glucoseor Aβ‐exposed RPE cells and in diabetic eyes, accompanying inhibition of RPE detachment from Bruch’s membrane. Adding eucalyptol to glucose‐ or Aβ‐loaded RPE cells, and diabetic mouse eyes reciprocally reversed induction/activation of apoptosis‐related bcl‐2, bax, cytochrome C/Apaf‐1 and caspases. Eucalyptol attenuated the generation of reactive oxygen species and the induction of receptor for advanced glycation end products in Aβ‐exposed RPE cells and diabetic eyes. Eucalyptol may ameliorate RPE barrier dysfunction in diabetic eyes through counteracting Aβ‐mediated oxidative stress‐induced RPE cell apoptosis.