Increased extracellular matrix metalloproteinase inducer (EMMPRIN) expression in the conjunctival epithelium exposed to antiglaucoma treatments.
OBJECTIVE
To analyze the effect of preserved antiglaucoma eye drops on the expression of extracellular matrix (ECM) metalloproteinase inducer (EMMPRIN) in conjunctival epithelial cells.


METHODS
A total of 18 patients treated for primary open-angle glaucoma with benzalkonium chloride (BAK) preserved eye drops and eight age-matched controls were included in this study. Glaucoma patients were divided into two groups according to their daily exposure to BAK: high-exposure (HE) group and low-exposure (LE) group. HLA-DR and EMMPRIN were quantified on conjunctival impression cytology specimens using flow cytometry. In parallel, IOBA-NHC conjunctival epithelial cells were exposed to different BAK concentrations, in the presence or absence of cyclosporine A (CsA), and their total and surface expressions of EMMPRIN were assessed by flow cytometry and results are given in relative fluorescence intensities (RFIs).


RESULTS
Compared to the control group (1.71 ± 0.39 RFI), EMMPRIN was significantly increased in the HE (4.19 ± 1.50 RFI, p < 0.001) and LE groups (2.55 ± 0.40 RFI, p = 0.029). Similar increase was observed in HLA-DR expression in the HE (4.58 ± 1.38 RFI, p < 0.001) and LE groups (2.52 ± 0.47 RFI, p = 0.046) as compared to control subjects (1.75 ± 0.27 RFI). Across all subjects enrolled in the study, there was a significant correlation between HLA-DR and EMMPRIN (R(2) = 0.875, p < 0.0001). IOBA-NHC cells exposed to BAK presented a significant increase in EMMPRIN, which was proportional to the concentration of BAK. The surface expression of EMMPRIN was inhibited by CsA.


CONCLUSIONS
The increased expression of EMMPRIN in patients topically treated with multiple antiglaucoma BAK-preserved eye drops suggests a matrix metalloproteinase-related modification of conjunctival ECM remodeling. In vitro results suggest that CsA has the potential to limit BAK effects on EMMPRIN.
Department of Ophthalmology, Quinze-Vingts National Ophthalmology Hospital, Paris and Ambroise Paré Hospital , AP-HP, Boulogne-Billancourt , France .
Antoine
A
Labbé
Eric
E
Gabison
Françoise
F
Brignole-Baudouin
Luisa
L
Riancho
Suzanne
S
Menashi
Christophe
C
Baudouin
D000368:Aged; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051926:Basigin / Q000378:metabolism*; D001548:Benzalkonium Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D003228:Conjunctiva / Q000187:drug effects* / Q000201:enzymology; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology; D005260:Female; D005434:Flow Cytometry; D005902:Glaucoma, Open-Angle / Q000188:drug therapy* / Q000201:enzymology; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology / Q000627:therapeutic use*
D000959:Antihypertensive Agents; C497886:BSG protein, human; D001548:Benzalkonium Compounds; D006684:HLA-DR Antigens; D011310:Preservatives, Pharmaceutical; D051926:Basigin
Antiglaucoma treatment; EMMPRIN; benzalkonium chloride; conjunctiva; preservatives