Purchase this article with an account.
SC Pflugfelder, W Farley, D-Q Li, X Song, E Fini; Matrix Metalloproteinase-9 (MMP-9) Knockout Alters the Ocular Surface Response to Experimental Dryness . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3124.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose:To investigate the role of MMP-9 in the pathophysiology of dry eye by comparing the reponse to experimental ocular surface dryness in a genetically-deficient mouse strain with matched littermates. Methods:Aqueous tear production and clearance were inhibited by subcutaneous scopolamine injection and exposure to an air draft for 12 days in 4-6 week old MMP-9 KO mice (BKO) and normal littermates (WT). MMP-9 in tear fluid was detected by gelatin zymography. Corneal permeability to 3 molecules of different molecular weights (MW): carboxyfluorescein (CF, MW 460), aIexafluor dextran (AFD, MW 10 kD) and horseradish peroxidase (HRP, MW 44 kD) were evaluated. Epithelial proliferation was assessed by BrDU labeling. Goblet cell density was evaluated in PAS-stained histological sections. CD11b (MAC1) positive leukocyte infiltration was assessed by immunofluorescent staining. Results:Treated WT mice developed a significant increase in tear MMP-9 concentration that was not observed in the BKO mice. Corneal epithelial permeability to all 3 molecules increased with induction of dry eye in both groups of mice and this increase was significantly greater in WT than BKO mice (P=0.002 for CF, P = 0.03 for AFD and P <0.05 for HRP). Dryness caused a significant increase in BrDU-labeled cells in the corneal and conjunctival (bulbar and tarsal) epithelium of both groups of mice and a significantly greater number (P<0.0001) of labeled cells in these tissues were observed in treated and untreated BKO mice compared to the WT. A significant decrease in conjunctival (cj) goblet cell (GC) density was noted in both groups of treated compared to untreated controls; however, GC loss was greater in the BKO than WT mice(P= 0.0002 for bulbar and P =0.04 for tarsal cj). A significantly greater number of CD11b+ cells (P< 0.004) infiltrated the cj and cornea of dry eye mice (WT and BKO) compared to controls and there was no difference between groups. Conclusion:The data support the hypothesis that MMP-9 contributes to the pathophysiology of dry eye.
This PDF is available to Subscribers Only