Abstract
Prostaglandin (PG) analogs, including latanoprost, travoprost, and bimatoprost, are currently the most commonly used topical ocular hypotensive medications. The purpose of this study was to investigate the corneal alterations in rabbits following exposure to commercial solution of latanoprost, travoprost and bimatoprost. A total of 64 New Zealand albino rabbits were used and four groups of treatments were constituted. Commercial latanoprost, travoprost, bimatoprost or 0.02% benzalkonium chloride (BAK) was applied once daily to one eye each of rabbits for 30 days. The contralateral untreated eyes used as controls. Schirmer test, tear break-up time (BUT), rose Bengal and fluorescein staining were performed on days 5, 10, 20, and 30. Central corneal changes were analyzed by in vivo confocal microscopy, and the corneal barrier function was evaluated by measurement of corneal transepithelial electrical resistance on day 5. Whole mount corneas were analyzed by using fluorescence confocal microscopy for the presence of tight-junction (ZO-1, occludin) and adherens-junction (E-cadherin, β-catenin) proteins, actin cytoskeleton, proliferative marker Ki67 and cell apoptosis in the epithelium. Topical application of commercial PG analogs resulted in significant corneal epithelial and stromal defects while no significant changes in aqueous tear production, BUT, rose bengal and fluorescein staining scores on day 5. Commercial PG analogs induced dislocation of ZO-1 and occludin from their normal locus, disorganization of cortical actin cytoskeleton at the superficial layer, and disruption of epithelial barrier function. The eyes treated with 0.02% BAK and latanoprost exhibited significantly reduced Schirmer scores, BUT, and increased fluorescein staining scores on days 10 and 30, respectively. Topical application of commercial PG analogs can quickly impair the corneal epithelium and stroma without tear deficiency. Commercial PG analogs break down the barrier integrity of corneal epithelium, concomitant with the disruption of cell junction and actin cytoskeleton between superficial cells in the corneal epithelium in vivo.
Highlights
The corneal epithelium provides a physical and functional barrier that protects the eye from harmful external agents, such as microbes and chemicals, and contributes to the transparency of the cornea [1,2,3]
Clinical Findings The travopost and bimatoprost groups showed no statistical differences in aqueous tear production, break-up time (BUT), corneal fluorescein and rose bengal scores compared with the control group at each time point
We have shown that optical application of commercial PG analogs can quickly break down the barrier integrity of corneal epithelium without causing significant changes in aqueous tear production, corneal fluorescein and Rose bengal scores, and BUT
Summary
The corneal epithelium provides a physical and functional barrier that protects the eye from harmful external agents, such as microbes and chemicals, and contributes to the transparency of the cornea [1,2,3]. TJs are composed of zonula occludens (ZO)-1, ZO2, ZO-3, occluden, claudin, and junctional adhesion molecules, which interact with their counterparts in the neighboring cells. The cytoplasmic domains of the transmembrane molecules of TJs and of the AJs are structurally and functionally linked to the actin cytoskeleton via adapter molecules, such as ZO-1, ZO-2, and b-catenin. These cell junctional proteins have been shown to be important for corneal epithelial barrier function[8]
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