title: Efficacy of a New Ocular Surface Modulator in Restoring Epithelial Changes in an In Vitro Model of Dry Eye Syndrome.
abstract: So far tear substitutes have demonstrated a limited role in restoring ocular surface damage in dry eye syndrome (DES). The aim of this study was to assess the efficacy of a new ocular surface modulator in an in vitro model of human corneal epithelium (HCE) damaged by severe osmotic stress mirroring the features of dry eye conditions.
  
  
  
  A reconstructed HCE model challenged by the introduction of sorbitol in the culture medium for 16 h was used to induce an inflammatory pathway and to impair the tight junctions integrity determining a severe modification of the superficial layer ultrastructure. At the end of the overnight stress period in the treated HCE series, 30 μl of the ocular surface modulator (T-LysYal, Sildeha, Switzerland) and of hyaluronic acid (HA) in the control HCE series were applied for 24 h. The following parameters were quantified: scanning electron microscopy (SEM), trans-epithelial electrical resistance (TEER), immunofluorescence analysis of integrin β1 (ITG-β1), mRNA expression of Cyclin D-1 (CCND1), and ITG-β1.
  
  
  
  In the positive control after the osmotic stress the HCE surface damage was visible at the ultrastructural level with loss of cell-cell interconnections, intercellular matrix destruction, and TEER reduction. After 24 h of treatment with T-LysYal, HCE showed a significant improvement of the ultrastructural morphological organization and increased expression of ITG-β1 at the tissue level when compared to positive and control series. A significant increase of mRNA expression for ITG-β1 and CCND1 was shown in the HA-treated cells compared to T-LysYal. TEER measurement showed a significant reduction in all groups after 16 h without modifications after the treatment period.
  
  
  
  This study has shown the possibility of a new class of agents denominated ocular surface modulators to restore corneal cells damaged by dry eye conditions. Further in vivo studies are certainly necessary to confirm these results.
authors.affiliation: a Clinica Oculistica, Di.N.O.G.M.I. , Azienda Ospedaliera Universitaria San Martino-IST, Genoa , Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Barabino
authors.affiliation: b VitroScreen SrL-in Vitro Research Laboratories , Milan , Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: De Servi
authors.affiliation: c Humanitas Mater Domini , Castellanza , Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Aragona
authors.affiliation: d Sildeha , Lugano , Switzerland.
authors.forename: Demetrio
authors.initials: D
authors.lastname: Manenti
authors.affiliation: b VitroScreen SrL-in Vitro Research Laboratories , Milan , Italy.
authors.forename: Marisa
authors.initials: M
authors.lastname: Meloni
mesh_terms: D002478:Cells, Cultured; D015352:Dry Eye Syndromes / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D017097:Electric Impedance; D019573:Epithelium, Corneal / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D006801:Humans; D008239:Lysine / Q000494:pharmacology*; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D012965:Sodium Chloride / Q000494:pharmacology*; D013666:Tears / Q000737:chemistry; D013941:Thymine / Q000494:pharmacology*; D019108:Tight Junctions / Q000378:metabolism / Q000648:ultrastructure
chemical_list: C000608691:T-LysYal; D012965:Sodium Chloride; D008239:Lysine; D013941:Thymine
keywords: Corneal epithelium; dry eye syndrome; inflammation; ocular surface modulator; scanning electron microscopy