March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
Modulation of Ocular Surface Barrier Function by Galectin-3
Author Affiliations & Notes
  • Jerome Mauris
    The Schepens, Mass Eye & Ear, Harvard Med School, Boston, Massachusetts
  • Flavio Mantelli
    The Schepens, Mass Eye & Ear, Harvard Med School, Boston, Massachusetts
  • Noorjahan A. Panjwani
    Department of Ophthalmology, Tufts University Medical School, Boston, Massachusetts
  • Pablo Argueso
    The Schepens, Mass Eye & Ear, Harvard Med School, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Jerome Mauris, None; Flavio Mantelli, None; Noorjahan A. Panjwani, None; Pablo Argueso, None
  • Footnotes
    Support  NIH Grant EY014847 (PA)
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 1842. doi:
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      Jerome Mauris, Flavio Mantelli, Noorjahan A. Panjwani, Pablo Argueso; Modulation of Ocular Surface Barrier Function by Galectin-3. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1842.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Efficient topical drug delivery into the anterior segment of the eye requires good corneal penetration. We previously reported that O-glycans on transmembrane mucins bind the ß-galactoside-binding protein galectin-3 on the apical corneal epithelium to maintain ocular surface barrier function. Here, we evaluated whether inhibition of galectin-3 binding could potentially be used to modulate barrier function at the ocular surface.

Methods: : Human corneal-limbal epithelial (HCLE) cells were grown in conditions that induce stratification and mucin biosynthesis. Rose bengal barrier function assays were performed on cells treated with one of the following: siRNA targeting galectin-3; recombinant galectin-3 (rGal3); competitive inhibitors of galectin-3 binding, including a dominant negative inhibitor of galectin-3 lacking the N-terminal domain (rGal3C), ß-lactose, or modified citrus pectin (MCP). Cell surface galectin-3 was detected using biotinylation assays and western blot. Rose bengal uptake was also evaluated in corneas of galectin-3 null and wild type mice.

Results: : Use of siRNA significantly reduced the levels of galectin-3 protein in stratified cultures of HCLE cells while increasing rose bengal uptake as compared to scramble control. Addition of rGal3C, but not rGal3, to cell culture media disrupted epithelial barrier function. Similarly, addition of ß-lactose and MCP increased dye penetrance and reduced the levels of cell surface galectin-3. Interestingly, the abrogation of barrier function was transient, as both dye penetrance and cell surface galectin-3 returned to basal levels within 4 h. Corneas of galectin-3 null mice showed increased dye penetrance as compared to wild-type.

Conclusions: : Competitive inhibition of galectin-3 binding results in transient disruption of the corneal epithelial barrier. It is, therefore, possible that galectin-3 binding inhibitors could be used therapeutically to enhance topical drug delivery.

Keywords: cornea: surface mucins • cornea: tears/tear film/dry eye • glycoconjugates/glycoproteins 

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