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0.01). The greatest reduction in corneal staining was observed in mice treated with arti?cial tears containing CMC+HA followed by HA only during both test regimens. The arti?cial tear formulation containing CMC+HA signi?cantly reduced corneal staining compared with formulations containing CMC only (P <
0.01) and HA only (P <
0.05) at day
14 (regimen 1;
Fig. 2a) and day
28 (regimen 2;
Fig. 2b). During regimen
2 (treatment regi- men), the arti?cial tear formulation containing HA only sig- ni?cantly decreased corneal staining compared with the formulation containing CMC only (P <
0.05;
Fig. 2b). Conjunctival goblet cell quanti?cation In the normal group of mice (not housed in the ICES chamber), the mean (Cstandard deviation) number of goblet cells was 193.5 C 11. Mice housed in the ICES chamber for
28 days (regimen 2) demonstrated more dramatic decreases in conjunctival goblet cells than mice housed for
14 days (regimen 1;
Fig. 3). Quantitatively, the number of goblet cells was greater in ICES-housed mice following treatment with arti?cial tear formulations containing CMC+HA, CMC only, or HA only compared with mice receiving PBS or NT (Fig. 4). Treatment with the arti?cial tear formulation con- taining CMC+HA resulted in signi?cantly higher numbers of goblet cells at day
14 (regimen 1;
Fig. 4a) and day
28 (regimen 2;
Fig. 4b) compared with formulations containing CMC only (P <
0.01) or HA only (P <
0.05). Day
0 Day
0 Corneal Staining Score (Mean ± SD) Corneal Staining Score (Mean ± SD) Day
14 Day
14 Day
28 0
2 4
6 8
10 12
14 16
18 20 CMC + HA CMC HA PBS NT * *
0 2
4 6
8 10
12 14
16 18
20 CMC + HA CMC HA PBS NT ** * ** a b FIG. 2. Mean corneal ?uorescein staining in mice (64 eyes, n = 32) housed in the ICES chamber. (a) Regimen 1: arti?cial tear formulations were administered to mice immediately after placement in the ICES dry eye chamber, and corneal staining was evaluated at days
0 and 14. (b) Regimen 2: arti?cial tear formulations were administered to mice after
14 days of initiating ICES-induced dry eye, and corneal staining was evaluated at days 0, 14, and
28 after continued exposure to the ICES chamber. Arrows indicate when administration of arti?cial tears was initiated for mice treated in regimen
1 and regimen 2. *P <
0.01;
**P <
0.05 between treatment groups compared on the same day. NOVEL ARTIFICIAL TEAR FOR DRY EYE
527 Discussion The ICES-induced murine model of dry eye employed in this study has been propose........