Role of Matrix Metalloproteinase 9 in Ocular Surface Disorders

Abstract

Objectives: (1) To explore the role and significance of Matrix Metalloproteinase 9 (MMP-9), a proteolytic enzyme, in various ocular surface diseases of inflammatory, infectious, and traumatic etiology (2), to further elucidate the molecular mechanisms responsible for its overexpression in ocular surface disease states, and (3) to discuss possible targets of therapeutic intervention. Methods: A literature review was conducted of primary sources from 1995 onward using search results populated from the US National Library of Medicine search database. Results: MMP-9 overexpression has been found in in vitro and in vivo models of dry eye disease (DED), corneal ulceration, microbial keratitis, corneal neovascularization, ultraviolet light-induced radiation, and a host of additional surface pathologies. MMP-9 is involved in an intricate signal transduction cascade that includes induction by many proinflammatory molecules including interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-a), nuclear factor kappa light chain enhancer of activated B cells (NF-kB), platelet-activating factor, activator protein 1 (AP-1), and transforming growth factor beta (TGF-B). MMP-9 expression is blunted by a diverse array of molecular factors, such as tissue inhibitors of metalloproteinases, cyclosporine A (CyA), PES_103, epigalloccatechin-3-gallate (EGCG), N-acetylcysteine (NaC), ascorbate, tetracyclines, and corticosteroids. Inhibition of MMP-9 frequently led to improvement of ocular surface disease. Conclusions: Novel insights into the mechanistic action of MMP-9 provide potential for new therapeutic modulations of ocular surface diseases mediated by its overexpression.

Case Series of Perforated Keratomycosis after Laser-Assisted In Situ Keratomileusis

“…Published reports on infections following LASIK found that severe visual acuity reductions were significantly more associated with keratomycosis rather than bacterial and mycobacterial infections [ 14 ]. Biomechanically weakening, lack of commercially available antifungal eye drops, usage of steroids [ 15 ], and delayed diagnosis might be held responsible for the aggressive course of fungal keratitis after LASIK. It is noteworthy to mention that the high rate of treatment failure in eyes with Aspergillus species may be attributed to the perpendicular growth pattern of fungal filaments that made the infection penetrate quickly deep into the corneal layers [ 12 ].…”

Alpha‐lipoic acid: A possible pharmacological agent for treating dry eye disease and retinopathy in diabetes

“…61,62 MMP-9 over expression has been shown in dry eye. 63 Kelch-like ECH-associated protein 1 (Keap1)-Nrf2-antioxidant response element pathway has a pivotal role in the regulation of expression of antioxidants genes, maintaining antioxidant status in the corneal epithelial cells and thus protecting ocular surface from the dry eye disease. 64,65 Therefore, activation of Nfr-2 in the corneal epithelial cells can indirectly increase the antioxidant defense such as SOD, CAT and GPx.…”

Case Series of Brittle Cornea Syndrome

“…Pediatric patients have a greater risk of postoperative inflammatory [9]. Postoperative steroid should be used cautiously in patients with brittle cornea syndrome due to the negative effects of steroids on collagen synthesis as well as the risk of secondary glaucoma development [10]. The management of comorbidities also becomes complicated by the graft.…”

“…Glaucoma is the leading cause of irreversible blindness postkeratoplasty [15] and is a leading cause of graft failure [10]. Glaucoma management in pediatric patients is challenging due to the lack of cooperation of these patients.…”