| Objective:To investigate the pathologic and ultrastructural changes of cornea and adjacent bulbar conjunctiva in Mooren's ulcer and to determine the distribution of extracellular matrixs,matrix metalloproteinases and tissue inhibitors of metalloproteinases in these tissues.Some guiding information to study on the immuno-pathogenesis and an efficient therapy are expected to be developed through exploring the pathologic characteristic of Mooren's ulcer local lesion. Methods: 1. The samples of cornea, limbal cornea and adjacent bulbar conjunctiva taken from 2 cases with active Mooren's ulcer after lamellar keratoplasty were divided into two parts.One part was used to study the pathologic changes by light microscopy ,the other was used to study the ultrastructural changes by transmission electron microscopy.The same kind samples taken from a Terrien's Marginal Degeneration were used as a control to compare the histopathologic characteristic. The specimens of cornea perforated lesion taken from patients of a bacterical corneal ulcer,a herps simplex corneal ulcer and a fungal corneal ulcer after penetrating keratoplasty were cut into ultrathinsections and were used as a control to compare the ultrastructural changes of corneal ulcer. 2. The specimens of cornea lesion and the adjacent bulbar conjunctiva obtained from 6 cases of active Mooren's ulcer after lamellar keratoplasty were studied by immunohistochemical technique. Bulbar conjunctivas adjacent to limbal and peripheral corneas remained by penetrating keratoplasty taken from 4 normal human eyes which were provided by third military medical university eye bank were as a control group.The expressions in cornea of collagen type â…¢,laminin, fibronectin,active forms of matrix metalloproteinase including MMP-1,2,3,9 and tissue inhibitor of metalloproteinase including TIMP-1,2 were detected by SABC indirect immunofluorescence technique. The positive staining was further analyzed by an image-processing software (Image-pro plus 4.5) and a statistical software( SPSS12.0).The distribution of MMP-1,2,3,9,TIMP-1,2 in conjunctivas was detected by S-P immunohistochemistral staining. Results: 1. Chronic immunity inflammation including lymphocytes and plasma cells infiltrating existed in bulbar conjunctiva and sclera of Mooren's ulcer.Corneal epithelium ,Bowman's membrane,anterior stroma and adjacent superficial sclera had been melted and the stromal collagen appeared disorganization.Besides these phenomena, it also can be found that active keratocytes migrated to the ulcer focal and the epithelial basement membrane of ulcer progressive edge had been destroyed while the epithelium and stroma still kept quiescent. 2. Collagen type â…¢was not detected in normal cornea, however, the staining can be seen in corneal stroma close to Mooren's ulcer focus. Laminin expressed faintly in basement membrane of normal cornea and the level of expression increased in basement membrane and Bowman's membrane of Mooren's ulcer. In normal corneal basement membrane, fibronectin located continuously;whereas in that of Mooren's ulcer, it can't be seen in all sections.In one of these sections fibronectin expressed in epithelium and in the others it expressed in stoma close to ulcer focus. 3. MMP-1,2,TIMP-1 expressed faintly in normal conjunctival epithelium. MMP-1,2 expressed in Mooren's ulcer conjunctival epithelium and MMP-9 can be seen in the stroma feebly. Only TIMP-1,2 were detected in normal cornea epithelium while MMP-1,2,3,9,TIMP-1,2 all were found in Mooren's ulcer cornea. MMP-2,TIMP-2 expressed in epithelium and MMP-3 expressed in stroma and MMP-1,9,TIMP-1 expressed in both epithelium and stroma. Conclusions: 1. Epithelial basement membrane of Mooren's ulcer may have some abnormality since it lacks of fibronectin and can be invaded firstly during ulcer progressing. It's valuable to explore its histological characteristic and clues to immuno-pathogenesis of Mooren's ulcer maybe could be found. 2. In active Mooren's ulcer cases, corneal lesion and corneal wound healing coexist,but the destructive reaction is greater than wound healing.Over-expression of MMP-9 and unbalanced regulation of MMPs/TIMPs may play an important role in thecornea ulcer of this stage. 3. Since it lacks of fibronectin in epithelial basement membrane of Mooren's ulcer, fibronectin eyedrop is beneficial to early Mooren's ulcer in addition to systemic immunosuppressor. At active stage,treatment with Zn2+ and specific MMP activity inhibitors may accelerate the wound healing and prevent the postoperative relapse.
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