Increased Matrix Metalloproteinase-2 and Matrix Metalloproteinase-3 Concentrations in Corneal Epithelium of Patients with Recurrent Corneal Erosions

Abstract

Purpose. To assess the role of selected matrix metalloproteinases in defective corneal re-epithelization in patients with recurrent corneal erosions. Subjects. The study group (group 1) included patients with recurrent corneal erosions qualified for phototherapeutic keratectomy. The group 1 was divided into two subgroups regarding the etiology of recurrent corneal erosions: group 1A, Cogan’s basement membrane dystrophy, and group 1B, trauma. The control group (group 2) included patients with healthy eyes qualified for Epi-Bowman Keratectomy. Methods. The analyzed material was the corneal epithelium collected during phototherapeutic keratectomy or Epi-Bowman Keratectomy in the study or control group, respectively. Matrix metalloproteinases concentration was determined by an immunohistochemical method using Human Magnetic Luminex® Assay. Results. The study revealed a statistically significantly higher concentration of matrix metalloproteinase-2 in group 1 compared to the control and a statistically significantly higher concentration of matrix metalloproteinase-3 in group 1 compared to the control. Conclusions. The results obtained in the study can prove that matrix metalloproteinase-2 and matrix metalloproteinase-3 having the ability to dissolve anchoring fibers and the corneal epithelial basement membrane could be responsible for epithelial instability and their accumulation in the corneal epithelium may induce recurrence of erosion.

Matrix Metalloproteinases and the Pathogenesis of Recurrent Corneal Erosions and Epithelial Basement Membrane Dystrophy

“…The first peak occurs in younger patients around 30 with post-traumatic RCEs, and the second peak concerns older patients around 50 with RCEs due to corneal dystrophy. These observations are consistent with results obtained in experimental studies [ 112 ]. There are no data on the variability of the prevalence by gender or ethnicity [ 97 , 105 , 111 , 113 ].…”

“…Based on our previous studies of MMP concentrations in the corneal epithelium of RCE patients [ 112 ], which detail the precise etiology of RCEs, comparative analysis of MMP-2 and MMP-3 concentrations in EBMD and traumatic RCEs, showed a trend towards higher concentrations in the former, which is an essential observation regarding the pathogenesis of this disease entity. The significantly higher concentrations of selected MMPs in the corneal epithelium of all patients compared to healthy individuals and the trend of higher MMP concentrations in EBMD compared to post-traumatic RCEs can be interpreted from a broader perspective.…”

“…Interestingly, a comparative analysis of patients with traumatic RCE and EBMD showed that MMP-2 levels were higher in those with EBMD. The differences in MMP-2 concentrations between the groups were not statistically significant, but the trend towards higher concentrations in the group of patients with EBMD was noticeable [ 112 ].…”

“…The peak of its maximum concentration at the site of injury occurs earlier than that of the other MMPs, is associated with re-epithelialization, and declines within a few weeks after injury when the basement membrane of the corneal epithelium is fully restored [ 58 , 61 , 122 ]. Our study evaluating the levels of MMPs in corneal epithelium from RCE patients collected during phototherapeutic keratectomy, i.e., in a period of disease remission, showed no evidence of MMP-9 in the samples tested [ 112 ]. The reason could be that the tissue was collected after the erosion had healed, suggesting that although MMP-9 is the first to be synthesized and secreted by corneal epithelial basal cells at the edge of the migrating epithelium after injury, thus controlling the resynthesis of the epithelial basement membrane by stimulating cells to migrate [ 58 , 61 , 73 , 122 ], its concentration level has little or no effect on the development of subsequent erosions [ 112 ].…”

“…Our study evaluating the levels of MMPs in corneal epithelium from RCE patients collected during phototherapeutic keratectomy, i.e., in a period of disease remission, showed no evidence of MMP-9 in the samples tested [ 112 ]. The reason could be that the tissue was collected after the erosion had healed, suggesting that although MMP-9 is the first to be synthesized and secreted by corneal epithelial basal cells at the edge of the migrating epithelium after injury, thus controlling the resynthesis of the epithelial basement membrane by stimulating cells to migrate [ 58 , 61 , 73 , 122 ], its concentration level has little or no effect on the development of subsequent erosions [ 112 ]. This appears to be an important issue, as some authors [ 118 , 123 ] recommend the systemic use of tetracycline, an MMP-9 inhibitor, to prevent recurrent corneal erosions.…”