Abstract
Purpose: :
Jun 102 is a new ophtalmic eye–drop composition containing ML–7 ( a specific MLCK inhibitor ) devoted to treat ocular surface inflammation due to allergy, dryness syndrome or benzalkonium chloride ( BAK ) preservatives. The present study was aimed to evaluate its local protective effect on the inflammation and the increase of corneal permeability induced by BAK.
Methods: :
Ocular instillation of 10 µL of BAK 0.5 % in PBS was performed on adult male Wistar rats. Eyes were rinced with sterilized water, 10 min. after BAK preceded by ocular instillation at T = – 24, –12 and – 0.5 hours of ( 10 µ L ) of Jun 102 ( ML–7 : 100 µg into a gel form ) or 10 µL of gel form as vehicle. All the animals were sacrified 6 hours after BAK instillation. Eyes were isolated for direct freezing ( histologic study ) or biotinylation of the surface proteins to evaluate tight junction permeability. Assessment of ocular surface inflammation was done after Sirius red staining by measuring the inflammatory cell infiltration by an histological quantitative analysis using a Nikon Eclipse microscope. The tight junction permeability was tested on sections stained with avidine, mounted in a Cappel fluorostab embedding medium for fluorescent microscopy.
Results: :
Instillation of BAK 0.5 % significantly increased the eye inflammation. The quantitative analysis showed a significant increase of the number of eosinophil and neutrophil polynuclears. Pretreatment with Jun 102 significantly reduced the inflammation ( P < 0.05 ). No effect on inflammation was noted with the vehicle alone. BAK instillation also thickened the fluorescent corneal front on freezing sections indicating an increase of tight junction permeability. Pretreatment with Jun 102 suppressed this alteration of the paracellular permeability by BAK instillation while no effect was seen with the vehicle.
Conclusions: :
This study indicates that inhibition of corneal cytoskeleton contraction by a MLCK inhibitor prevented BAK–induced ocular inflammatory response and that Jun 102 composition containing ML–7 may be a new original preparation in the treatment of ocular surface pathologies.
Keywords: cornea: epithelium • inflammation • cell adhesions/cell junctions