Synthesis pattern of matrix metalloproteinases (MMPs) and inhibitors (TIMPs) in human explant organ cultures after treatment with latanoprost and dexamethasone.

PURPOSE: To determine changes in production of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the ciliary body, the trabecular meshwork and the retinal pigment epithelium induced by both prostaglandins and corticosteroids. METHODS: Explant organ cultures were removed by a scleral incision 3 mm posterior to the limbus. Retinal pigment epithelium was grown to confluence. Organ and cell cultures were treated with latanoprost and/or dexamethasone for 72 h. The activity of MMP-2, -3 and -9 was assessed using zymography. The synthesis pattern of MMPs and TIMP-1 and -2 was identified using immunostaining. RESULTS: Treatment of explant organ cultures with 10 micrograms/ml of latanoprost induced a mean upregulation of MMP-2 by 36%, MMP-3 by 112% and MMP-9 by 156% as seen by zymography. Dexamethasone 500 nm reduced the amounts of secreted MMP-2 by 13%, MMP-3 by 69%. MMP-9 was not detectable in the media of corticosteroid-treated explant organ cultures. The addition of 10 micrograms/ml of latanoprost to dexamethasone-treated cultures increased MMP-2 by 14%, MMP-3 by 43% and MMP-9 by 49%. Using immunohistochemistry we found staining with antibodies against MMP-2, -3, -9 and TIMP-1 and -2 within the ciliary body, and only to a lesser degree in the trabecular meshwork. Latanoprost treatment caused an increase of 29% in MMP-2 (p < 0.0001), 98% in MMP-3 (p < 0.0001) and 108% in MMP-9 (p < 0.0001). Dexamethasone reduced the staining for MMP-2 by 32% (p < 0.0001), for MMP-3 by 33% (p < 0.0001) and for MMP-9 by 83% (p < 0.0001). Almost no change in staining for MMPs was detectable in the trabecular meshwork. Neither latanoprost treatment nor dexamethasone induced significant changes (p < 0.93) in the secretion of TIMPs. In the media of non-treated retinal pigment epithelium (RPE) cells the only MMP detected was MMP-2. RPE cells in culture did not respond to either treatment with a change in their MMP secretion. CONCLUSION: We detected a profound upregulation of both MMP-3 and MMP-9 and a mild induction of MMP-2 through latanoprost in the ciliary body, but not the trabecular meshwork or RPE cells. Corticosteroids, on the other hand, downregulated MMP expression in both tissues. This inhibiting effect of corticosteroids on MMP production was reversed by latanoprost.

Cutaneous myxoid fibroblastoma. A histological, immunohistochemical, and ultrastructural study.

A fibroblastic skin tumor with a myxoid matrix is reported that cannot be easily classified as one of the well-known entities of fibrous/fibrohistiocytic and myxoid skin tumors. A 27-year-old white woman presented with a reddish, dome-shaped cutaneous nodule 8 mm in diameter on the left popliteal fossa that had developed spontaneously within the preceding 2 years. There was no sign of recurrence 30 months after excision. Light microscopic examination showed a well-circumscribed tumor confined to the upper dermis and consisting of stellate and spindle-shaped cells arranged loosely in a fascicular pattern resembling tissue cultures of fibroblasts. There were almost no collagen bundles between tumor cells, and Mowry's staining showed large amounts of glycosaminoglycans. Immunohistochemical studies of the tumor cells showed reactivity only to vimentin, whereas markers of histiocytes, dermal dendrocytes, and neurogenic and myogenic differentiation were negative. By electron microscopy, the majority of tumor cells contained elliptical nuclei, but some tumor cells had conspicuous multisegmented nuclei with several large and small nuclear segments connected by thin nuclear bridges (labyrinth nuclei). Single fibrils were found within the interstitium; collagen fibers were rare. Histological and ultrastructural examinations identified tumor cells as fibroblasts. High cellularity distinguishes this tumor from cutaneous myxoma. We conclude that this lesion represents a newly recognized tumor of fibroblastic origin. The name cutaneous myxoid fibroblastoma is proposed.

Multinucleate cell angiohistiocytoma: a clinicopathological, immunohistochemical and ultrastructural study.

The term 'multinucleate cell angiohistiocytoma' was first introduced by Smith and Wilson Jones in 1985. We report the clinicopathological, immunohistological and ultrastructural findings observed in two patients. Multinucleate cell angiohistiocytoma occurs mainly in middle-aged women and is usually located at acral sites, particularly the distal extremities. Grouped, brown-red, slightly elevated, asymptomatic papules slowly develop over several months until further growth ceases. There is no evidence of systemic disease. Histologically, the dermis shows numerous well developed capillaries with prominent endothelia, large bizarre basophilic and often multinucleate cells with a sparse lymphohistiocytic infiltrate. The immunohistological and ultrastructural findings suggest a fibroblastic differentiation of the large multinucleate cells.