Objective: To investigate the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the sclera of lamina cribrosa in rat chronic elevated intraocular pressure (IOP) and its the relationship with the pathogenesis of glaucoma.
Methods: It was an experimental study. Chronic ocular hypertension (OHT) model was induced in the left eyes of 43 Wistar rats by cauterizing episcleral venous while the right eyes were used as control. The rats were divided into three groups: 13 for immunohistology, 15 for Western blotting, and 15 for RT-PCR by randomly computerized assignment and sacrificed at week 12 after OHT induction. The expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 in the sclera lamina cribrosa was detected using immunohistology, Western blotting, and RT-PCR technique, respectively. Repeated measures ANOVA of two-factor Studies in SAS statistic software were used to analyze the data.
Results: After 12 weeks, compared with control eyes, the IOP of rat OHT eyes was significantly (F = 1519.67, P < 0.01) elevated. The expression of MMP-2 and MMP-9 was increased in cell nucleus and cytoplasm in sclera lamina cribrosa in rat OHT when compared to control eyes with negative expression. No expressions of TIMP-1, TIMP-2 in sclera lamina cribrosa were found in both OHT and control eyes. The mean gray-scale values of MMP-2, MMP-9, TIMP-1, and TIMP-2 in OHT were significantly (F = 405.55, F = 436.11, F = 1167.77, and F = 4629.64, P < 0.01) higher than control eye by Western blotting (193.88 +/- 8.84 vs 117.38 +/- 10.76, 202.65 +/- 8.37 vs 134.13 +/- 5.06, 283.63 +/- 5.65 vs 186.88 +/- 7.14, and 284.75 +/- 5.50 vs 183.0 +/- 5.58), while by RT-PCR (200.50 +/- 3.25 vs 181.88 +/- 9.36, 200.13 +/- 2.95 vs 181.75 +/- 5.85, 201.88 +/- 3.14 vs 179.25 +/- 9.21, and 195.50 +/- 3.55 vs 179.75 +/- 7.12), respectively.
Conclusion: The increased expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 in lamina cribrosa in rat OHT eye indicates that MMPs and TIMPs may be involved in the pathogenesis of glaucoma.