Matrix Metalloproteinase-2 Is Expressed in Melanoma-Associated Spongiform Scleropathy

Alyahya, Ghassan Ayish; Kolko, Miriam; Prause, Jan Ulrik; Nielsen, Boye Schnack; Wang, Jinmei; Heegaard, Steffen

doi:10.1167/iovs.07-1436

Cited by 9 publications

(7 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both MMP2 and MMP3 were shown to be expressed by resident scleral fibroblasts as well as inflammatory cells such as macrophages and T lymphocytes in necrotizing scleritis (Di Girolamo et al 1997 ). MMP2 was found to be expressed in samples of human melanoma-associated spongiform scleropathy, whereas MMP13 could not be detected in this study (Alyahya et al 2008 ). In tendon, MMPs are well described to be involved in matrix remodelling and degeneration in tendinopathy, causing collagen fibre disruption and tissue weakening (Riley 2008 ).…”

Section: Discussionmentioning

confidence: 48%

Scleraxis expressing scleral cells respond to inflammatory stimulation

Atta

Schroedl

Kaser-Eichberger

et al. 2021

Histochem Cell Biol

View full text Add to dashboard Cite

The sclera is an ocular tissue rich of collagenous extracellular matrix, which is built up and maintained by relatively few, still poorly characterized fibroblast-like cells. The aims of this study are to add to the characterization of scleral fibroblasts and to examine the reaction of these fibroblasts to inflammatory stimulation in an ex vivo organotypic model. Scleras of scleraxis-GFP (SCX-GFP) mice were analyzed using immunohistochemistry and qRT-PCR for the expression of the tendon cell associated marker genes scleraxis (SCX), mohawk and tenomodulin. In organotypic tissue culture, explanted scleras of adult scleraxis GFP reporter mice were exposed to 10 ng/ml recombinant interleukin 1-ß (IL1-ß) and IL1-ß in combination with dexamethasone. The tissue was then analyzed by immunofluorescence staining of the inflammation- and fibrosis-associated proteins IL6, COX-2, iNOS, connective tissue growth factor, MMP2, MMP3, and MMP13 as well as for collagen fibre degradation using a Collagen Hybridizing Peptide (CHP) binding assay. The mouse sclera displayed a strong expression of scleraxis promoter-driven GFP, indicating a tendon cell-like phenotype, as well as expression of scleraxis, tenomodulin and mohawk mRNA. Upon IL1-ß stimulation, SCX-GFP+ cells significantly upregulated the expression of all proteins analysed. Moreover, IL1-ß stimulation resulted in significant collagen degradation. Adding the corticosteroid dexamethasone significantly reduced the response to IL1-ß stimulation. Collagen degradation was significantly enhanced in the IL1-ß group. Dexamethasone demonstrated a significant rescue effect. This work provides insights into the characteristics of scleral cells and establishes an ex vivo model of scleral inflammation.

show abstract

Section: Discussionmentioning

confidence: 48%

Scleraxis expressing scleral cells respond to inflammatory stimulation

Atta

Schroedl

Kaser-Eichberger

et al. 2021

Histochem Cell Biol

View full text Add to dashboard Cite

show abstract

“…To our knowledge, there has been no previously published illustration showing the staining properties of these stains in melanoma-associated sponiform scleropathy. The implications of the finding in this case are unknown, as the mechanism(s) and clinical significance of melanoma-associated spongiform scleropathy are partially understood [9] . There is evidence that the collagen changes in melanoma-associated spongiform scleropathy may predispose to scleral invasion and possibly contribute to a less favorable outcome [1][2][3][4] .…”

Section: Discussionmentioning

confidence: 92%

“…The majority of research on melanoma-associated spongiform scleropathy has come from a single institution, and the finding has rarely been reported by others [1,2,9] . The pre-enucleation ultrasound biomicroscopic features of melanoma-associated spongiform scleropathy have been reported once [10] .…”

Section: Discussionmentioning

confidence: 98%

Melanoma-Associated Spongiform Scleropathy in Oculodermal Melanocytosis with Primary Orbital Melanoma

2016

View full text Add to dashboard Cite

Purpose: To describe spongiform scleropathy in a patient with oculodermal melanosis and without evidence of uveal melanoma. Methods: Clinical-pathological correlation conducted in compliance with HIPPA (Health Insurance Privacy and Portability Act) regulations. Results: Melanoma-associated spongiform scleropathy was an incidental finding in an 87-year-old woman with oculodermal melanocytosis treated for primary orbital melanoma. All previously reported cases of this scleropathy have been associated with uveal melanoma. Conclusions: The mechanism of scleral degeneration in melanoma-associated spongiform scleropathy is unknown, and its clinical and prognostic significance is speculative. This is the first case of a so-called melanoma-associated spongiform scleropathy reported in an eye without uveal melanoma.

show abstract

“…Another possible pathogenetic factor for the occurrence of SCD in UM eyes parallels the process seen in melanomaassociated spongiform scleropathy, 32 a noninflammatory deg-radation of the scleral collagen bundles with spongiotic structures observed in UMs. Matrix metalloproteinases, synthesized by the melanoma cells and/or by the melanoma stromal fibroblasts, act as the major mediators of disintegration of scleral collagen bundles into loose fibers in melanoma-associated spongiform scleropathy.…”

Section: Discussionmentioning

confidence: 93%

The Occurrence and Proposed Significance of Schnabel Cavernous Degeneration in Uveal Melanoma

et al. 2014

View full text Add to dashboard Cite

veal melanoma (UM) is the most common primary intraocular malignant neoplasm in adults, occurring in 7 per million per year in the United States. 1 Multiple chromosomal abnormalities such as monosomy 3 and several genetic mutations have been reported in association with this tumor. [2][3][4][5] UV light, environmental factors, trauma, and viruses 6-10 have been implicated as the underlying cause. Furthermore, uveal nevus, congenital ocular or oculodermal melanocytosis, and benign diffuse uveal melanocytic proliferation have been suggested as predisposing factors. [11][12][13][14] It remains uncertain whether there is an association between Schnabel cavernous degeneration (SCD) and UMs. Schnabel cavernous degeneration is a rare histopathologic en-tity that appears as rarefaction and spongiform degeneration of the optic nerve substance posterior to the lamina cribrosa. Associated with a loss of myelin and axons, it is characterized by the presence of hyaluronidase-sensitive acid mucopolysaccharides within the cavernous spaces. [15][16][17] In a case report by Albert and colleagues, 18 a bilateral SCD of undetermined origin was found in a 26-year-old man with bilateral metastatic UM and no history of glaucoma. Sudden and pronounced elevation of intraocular pressure, forcing the vitreous into the cavernous spaces, was historically the main proposed mechanism for SCD. [19][20][21][22][23][24][25] Subsequently, marked reduction of blood flow of the optic nerve head and resultant ischemia have been proposed as the most important factors in SCD. 20 In a large case IMPORTANCE Schnabel cavernous degeneration (SCD) has been observed in eyes with uveal melanoma (UM), but, to our knowledge, a definitive study establishing the association between SCD and UM has not been conducted.OBJECTIVE To explore an association between SCD and UM. DESIGN, SETTING, AND PARTICIPANTSA historical cohort analysis was performed using histologic slides and related clinical records of cases from the Collaborative Ocular Melanoma Study and Eye Pathology Laboratory at the University of Wisconsin, including 1985 UM eyes, 517 eye bank eyes, and 155 enucleated glaucomatous eyes. MAIN OUTCOMES AND MEASURESThe prevalence of SCD was calculated and compared between each group; subgroup analysis was also conducted of eyes with and without SCD for the prevalence of glaucoma.RESULTS Schnabel cavernous degeneration was seen in 17 (0.9%) UM eyes, 9 (1.7%) eye bank eyes, and 2 (1.3%) enucleated glaucomatous eyes. No difference was detected between the prevalence of SCD in UM eyes and eye bank eyes (odds ratio [OR], 0.49; 95% CI, 0.22-1.10) or enucleated glaucomatous eyes (OR, 0.66; 95% CI, 0.15-2.89). Subgroup analysis, performed on 421 UM eyes, provided sufficient clinical information to definitively establish the presence or absence of glaucoma. Of the 95 (22.6%) eyes with glaucoma, 11 (11.6%) revealed histopathologic evidence of SCD. Compared with enucleated end-stage glaucoma eyes, this represents a 10-fold increase in SCD in UM eyes with glaucoma (OR, 10.10...

show abstract

Matrix Metalloproteinase-2 Is Expressed in Melanoma-Associated Spongiform Scleropathy

Cited by 9 publications

References 31 publications

Scleraxis expressing scleral cells respond to inflammatory stimulation

Scleraxis expressing scleral cells respond to inflammatory stimulation

Melanoma-Associated Spongiform Scleropathy in Oculodermal Melanocytosis with Primary Orbital Melanoma

The Occurrence and Proposed Significance of Schnabel Cavernous Degeneration in Uveal Melanoma

Contact Info

Product

Resources

About