Table 3.
MMP and TIMP expression upon free acid PGA treatment of bimatoprost (A), latanoprost (B), and unoprostone (C) in conditioned media of human TM endothelial cells incubated at the suprapharmacologic concentrations of 0.1 μg/ml, 0.3 μg/ml, and 1.45 μg/ml respectively, for 24 hours.
| A. Bimatoprost Free Acid Suprapharmacologic Concentrations | ||||||
| MMPs/TIMP | ↑/↔ /↓ | Trend | % Change of Trend | % Change of All Samples | N | P-Value |
| MMPs | ||||||
| Pro-MMP-1 | 1/4/0 | ↔ | (12 ± 13%) | (15 ± 14%) | 5 | 0.1287 |
| Pro-MMP-2 | 0/5/0 | ↔ | (4 ± 5%) | (4 ± 5%) | 5 | 0.4468 |
| Pro-MMP-3 | 3/2/0 | ↑ | (41 ± 13%) | (34 ± 15%) | 5 | 0.0072 |
| Pro-MMP-9 | 3/2/0 | ↑ | (121 ± 38%) | (60 ± 45%) | 5 | 0.0680 |
| MMP-24(CL) | 2/2/1 | Ind. | (4 ± 8%) | (4 ± 8%) | 5 | 0.5047 |
| Active MMPs | ||||||
| Inter MMP-1 | 1/4/0 | ↔ | (3 ± 8%) | (4 ± 9%) | 5 | 0.5249 |
| Active MMP-2 | 0/5/0 | ↔ | (6 ± 8%) | (6 ± 8%) | 5 | 0.3254 |
| Active MMP-9 | 4/1/0 | ↑ | (14 ± 2%) | (15 ± 3%) | 5 | 0.0124 |
| TIMPs | ||||||
| TIMP-1 | 3/2/0 | ↑ | (60 ± 27%) | (35 ± 30%) | 5 | 0.1023 |
| TIMP-2 | 3/2/0 | ↑ | (38 ± 18%) | (25 ± 20%) | 5 | 0.0835 |
| TIMP-3 | 0/2/3 | ↓ | (−30 ± 4%) | (−3 ± 10%) | 5 | 0.6479 |
| TIMP-4 | 4/1/0 | ↑ | (90±13%) | (80 ± 17%) | 5 | 0.0001 |
| B. Latanoprost Free Acid Suprapharmacologic Concentrations | ||||||
| MMPs/TIMP | ↑/↔ /↓ | Trend | % Change of Trend | % Change of All Samples | N | P-Value |
| MMPs | ||||||
| Pro-MMP-1 | 4/1/0 | ↑ | (33 ± 12%) | (30 ± 15%) | 5 | 0.0134 |
| Pro-MMP-2 | 0/5/0 | ↔ | (3 ± 5%) | (3 ± 5%) | 5 | 0.5651 |
| Pro-MMP-3 | 2/3/0 | ↔ | (6 ± 13%) | (12 ± 13%) | 5 | 0.1826 |
| Pro-MMP-9 | 4/1/0 | ↑ | (60 ± 24%) | (37 ± 25%) | 5 | 0.0474 |
| MMP-24(CL) | 0/4/1 | ↔ | (−3 ± 4%) | (−5 ± 6%) | 5 | 0.3658 |
| Active MMPs | ||||||
| Inter MMP-1 | 4/1/0 | ↑ | (14 ± 1%) | (12 ± 2%) | 5 | 0.0301 |
| Active MMP-2 | 0/5/0 | ↔ | (5 ± 2%) | (5 ± 2%) | 5 | 0.3048 |
| Active MMP-9 | 3/2/0 | ↑ | (18 ± 4%) | (14 ± 6%) | 5 | 0.0277 |
| TIMPs | ||||||
| TIMP-1 | 0/2/3 | ↓ | (−29 ± 3%) | (−15 ± 10%) | 5 | 0.0451 |
| TIMP-2 | 3/2/0 | ↑ | (20 ± 5%) | (15 ± 7%) | 5 | 0.0251 |
| TIMP-3 | 2/1/2 | Ind. | (9 ± 7%) | (9 ± 7%) | 5 | 0.1378 |
| TIMP-4 | 4/1/0 | ↑ | (76 ± 37%) | (55 ± 35%) | 5 | 0.0378 |
| C. Unoprostone Free Acid Suprapharmacologic Concentrations | ||||||
| MMPs/TIMP | ↑/↔ /↓ | Trend | % Change of Trend | % Change of All Samples | N | P-Value |
| MMPs | ||||||
| Pro-MMP-1 | 3/2/0 | ↑ | (45 ± 26%) | (37 ± 28%) | 5 | 0.0701 |
| Pro-MMP-2 | 0/5/0 | ↔ | (−6 ± 2%) | (−6 ± 2%) | 5 | 0.2248 |
| Pro-MMP-3 | 3/2/0 | ↑ | (15 ± 27%) | (13 ± 25%) | 5 | 0.4348 |
| Pro-MMP-9 | 3/2/0 | ↑ | (86 ± 10%) | (41 ± 19%) | 5 | 0.0092 |
| MMP-24(CL) | 0/4/1 | ↔ | (−3 ± 8%) | (−5 ± 9%) | 5 | 0.4301 |
| Active MMPs | ||||||
| Inter MMP-1 | 2/3/0 | ↔ | (7 ± 2%) | (10 ± 5%) | 5 | 0.0805 |
| Active MMP-2 | 0/5/0 | ↔ | (1 ± 2%) | (1 ± 2%) | 5 | 0.8319 |
| Active MMP-9 | 0/5/0 | ↔ | (5 ± 5%) | (5 ± 5%) | 5 | 0.3466 |
| TIMPs | ||||||
| TIMP-1 | 3/2/0 | ↑ | (93 ± 32%) | (68 ± 53%) | 5 | 0.0770 |
| TIMP-2 | 3/2/0 | ↑ | (59 ± 33%) | (32 ± 37%) | 5 | 0.2087 |
| TIMP-3 | 3/0/2 | ↑ | (29 ± 14%) | (4 ± 33%) | 5 | 0.8528 |
| TIMP-4 | 3/2/0 | ↑ | (151 ± 70%) | (70 ± 58%) | 5 | 0.0928 |
For MMP-24, the protein extracted from cell lysate was used. Different cell lines were used for each experiment. The data represents determination of effect (↑, ↓, ↔, ind); # of samples with densitometry greater than 10% of the respective control / # of samples within 10% of the control/ and # of samples with densitometry lower than 10% of the control; (average % increase or decrease ± std error); ind is indeterminate. The % change of all samples refers to the mean of all samples tested. The % change of trend refers to the mean of the samples that were directionally consistent with the overall results.