Safety of Using Matrix Metalloproteinase Inhibitor in Experimental Glaucoma Filtration Surgery

Abstract

We evaluated the safety of matrix metalloproteinase (MMP) inhibitor in experimental glaucoma filtration surgery in an animal model. Fifteen New Zealand white rabbits underwent an experimental trabeculectomy and were randomly allocated into 3 groups according to the adjuvant agent: no treatment group (n = 5), 0.02% mitomycin C (MMC) soaking group (n = 5), and MMP inhibitor (ilomastat) subconjunctival injection group (n = 5). Slit lamp examination with Seidel testing, pachymetry, and specular microscopy was performed preoperatively and postoperatively. The conjunctiva and ciliary body toxicity were evaluated with scores according to the pathologic grading systems. Electron microscopy was used to examine the structural changes in cornea, conjunctiva, and ciliary body. In the ilomastat-treated group, there was no statistically significant change in central corneal thickness preoperatively and at 28 days postoperatively (P = 0.655). There were also no significant changes in specular microscopy findings over the duration of the study in the ilomastat-treated group. The conjunctival toxicity score was 1 in the control group, 1.5 in the ilomastat-treated group, and 2 in the MMC-treated group. When assessing ciliary body toxicity scores, the ilomastat-treated group score was 0.5 and the MMC-treated group score was 1.5. Transmission electron microscopy did not show structural changes in the cornea and ciliary body whereas the structural changes were noticed in MMC group. A single subconjunctival injection of MMP inhibitor during the experimental trabeculectomy showed a less toxic affect in the rabbit cornea, conjunctiva, and ciliary body compared to MMC.

Keywords: Filtration; Glaucoma; Matrix Metalloproteinase Inhibitor.

Fig. 1

Specular microscopy of corneal endothelial cells of the rabbits on postoperative 28 days. (A) Control group. (B) Ilomastat treated group. (C) Mitomycin-treated group. In the ilomastat-treated group, there was no statistically significant differences in all parameters preoperatively and at postoperative 28 days.

Fig. 2

Transmission electron microscopic view of cornea. (A, D, G) Control group. (B, E, H) Ilomastat-treated group. (C, F, I) Mitomycin-treated group. (A) The stratified squamous nonkeratinized epithelium resting on Bowman's membrane was noticed. Wing cells and basal low columnar cells with oval nuclei were observed. Interdigitation and junctional complexes at the lateral surface of basal epithelial cells were noticed. (B) Variable-sized vacuoles were observed in cytosplsm and loss of junctional complexes at lateral side was observed in basal cells. (C) Cellular integrity was maintained and surface damage or cellular desquamation resulting from toxicity was not observed. Microvilli on superficial cells were well preserved. (D) Normal long spindle shaped keratocyte are scattered among the lamellae of the stroma and the structures in the cytoplsam were well preserved. (E) Multiple vacuoles were observed in the cytoplasm of keratocyte. (F) A normal-looking spindle-shaped keratocyte was observed. Numerous well-preserved rough endoplasmic reticulum was noticed. (G) A thick homogenous noncellular Descemet's membrane lined by a single endothelial cell layer with a moderate electron-dense oval nucleus. (H) Intracytoplasimc multiple vacuoles are observed in corneal endothelial cell in MMC-treated group. MMC = Mitomycin C.