Corneal alterations induced by topical application of commercial latanoprost, travoprost and bimatoprost in rabbit

PLoS One. 2014 Mar 14;9(3):e89205. doi: 10.1371/journal.pone.0089205. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Amides / administration & dosage*
  • Amides / pharmacology*
  • Animals
  • Bimatoprost
  • Cloprostenol / administration & dosage
  • Cloprostenol / analogs & derivatives*
  • Cloprostenol / pharmacology
  • Cornea / drug effects
  • Latanoprost
  • Male
  • Prostaglandins F, Synthetic / administration & dosage*
  • Prostaglandins F, Synthetic / pharmacology*
  • Rabbits
  • Travoprost

Substances

  • Amides
  • Prostaglandins F, Synthetic
  • Cloprostenol
  • Latanoprost
  • Bimatoprost
  • Travoprost

Grants and funding

This work was supported by the National Natural Science Foundation of China, Beijing, China (grant no 81270978, U1205025, 81330022, 30973249, 81100638); Medical Innovative Program of Fujian Province, China (grnat no 2012-CXB-31); Science and Technology Planning Projects of Xiamen (No. 3502Z20094027, No. 3502Z20131017); and Health Department Project of Fujian (No. 2013-2-112). The funders had no role in study design, data collection and analysis, decision on publish, or preparation of the manuscript.