Uveal Melanoma Metastasis Models

Ophthalmic researc

Helicobacter pylori (H. pylori) molecular signature in conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma

Conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma is an extranodal marginal zone B-cell lymphoma that is characterized by an exaggerated clonal expansion of B cells, which implicate a pathological proliferative response to antigen(s) including bacteria. Helicobacter pylori (H. pylori) infection is recognized as one of the causative agents of gastric MALT lymphoma; however, it has not been reported in extra gastric MALT lymphoma. We studied 5 patients (4 adults and 1 child) with salmon-colored conjunctival lesions. One patient also had a history of abnormal bone marrow biopsy a year earlier with lymphoid aggregates involving 5% of the overall bone marrow. The conjunctival lesions of the 5 patients were biopsied. Histopathological diagnoses were consistent with conjunctival MALT lymphoma. Lymphoma and normal conjunctival cells were microdissected using laser capture microscopy or manual techniques. DNA was extracted and subjected to PCR amplification using H. pylori gene-specific primers from the urease B and vac/m2 gene. Cells from chronic conjunctivitis (normal lymphocytes), conjunctival human T-cell lymphotropic virus type-1/adult T-cell leukemia/lymphoma (HTLV- 1/ATL), and orbital B-cell lymphoma were also microdissected, processed and analyzed. PCR amplification and Southern blot hybridization demonstrated H. pylori DNA in the conjunctival MALT lymphoma cells of 4/5 cases. The negative case was the one with a history of abnormal bone marrow. In contrast, H. pylori gene was not detected in normal conjunctival cells from the cases of MALT lymphoma or the lymphocytes, ATL and orbital B-lymphoma cells from the controls. These data suggest that H. pylori may play a role in conjunctival MALT lymphoma

Association of Uveal Melanoma Metastatic Rate With Stochastic Mutation Rate and Type of Mutation

Ophthalmic researc

Deposits of transforming growth factor-beta-induced protein in granular corneal dystrophy type II after LASIK.

PURPOSE: To analyze components of the deposits in the corneal flap interface of granular corneal dystrophy type II (GCD II) patients after laser in situ keratomileusis (LASIK). METHODS: Four corneal GCD II specimens displaying disease exacerbation after LASIK were analyzed. Three of these specimens included the recipient corneal button after penetrating keratoplasty or deep lamellar keratoplasty for advanced GCD II after LASIK. The fourth specimen, a similar case of GCD II after LASIK, included the amputated corneal flap. Specimens were processed for histopathologic and immunohistochemical analyses. RESULTS: Corneal stromal deposits in the LASIK flaps of all specimens were stained with 3 anti-transforming growth factor-beta-induced protein (TGFBIp) antibodies. The deposits displayed bright red color staining with Masson trichrome; however, negative staining was seen with Congo red, suggesting that hyaline is the main component localizing to the TGFBIp deposits rather than amyloid. CONCLUSIONS: Amorphous granular material deposited along the interface of the LASIK flap in GCD II corneas is composed mainly of hyaline deposits

Bevacizumab and intraocular tumors: an intriguing paradox

PURPOSE Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor-A (VEGF-A), was originally developed as an anti-tumor treatment. In ocular oncology, it is being used to treat macular edema due to radiation retinopathy, but it may also be useful for the treatment of primary uveal melanoma (UM) or its metastases. We determined the effect of bevacizumab on the growth of B16F10 cells inside the eye and on B16F10 and UM cells cultured in vitro. METHODS B16F10 melanoma cells were placed into the anterior chamber of the eye of C57Bl/6 mice and tumor growth was monitored after injection of different doses of bevacizumab or mock injection. In addition, the effect of bevacizumab on in vitro growth of B16F10 and human UM cells and on the expression of VEGF-A, GLUT-1, and HIF-1α was evaluated. RESULTS Following intraocular injection of bevacizumab into murine B16 tumor-containing eyes, an acceleration of tumor growth was observed, with the occurrence of anterior chamber hemorrhages. Bevacizumab did not affect proliferation of B16F10 cells in vitro, while it inhibited UM cell proliferation. Expression analysis demonstrated that addition of bevacizumab under hypoxic conditions induced VEGF-A, GLUT-1 and HIF-1α in B16F10 cells as well as in UM cell lines and two of four primary UM tumor cultures. CONCLUSIONS In contrast with expectations, intraocular injection of bevacizumab stimulated B16F10 melanoma growth in murine eyes. In vitro exposure of B16 and human UM cells to bevacizumab led to paradoxical VEGF-A upregulation. The use of VEGF inhibitors for treatment of macular edema (due to radiation retinopathy) after irradiation of UM should be considered carefully, because of the possible adverse effects on residual UM cells.Ophthalmic researc