ABSTRACT
PURPOSE: To report the clinical and histopathologic findings of limbal juvenile xanthogranuloma (JXG) in two children. METHODS: Case report. RESULTS: Two children (a 9-month old boy and a 4-year old girl) presented with an enlarging yellowish mass at the corneoscleral limbus. The girl had been diagnosed with neurofibromatosis 1 (NF1). Both lesions underwent simple excision. Histopathologic examination revealed foamy histiocytes within an inflammatory infiltrate with the presence of multiple multinucleated giant cells. In both cases intraoperative subconjunctival steroids and postoperative topical steroids were administered during 1 month. CONCLUSIONS: Juvenile xanthogranuloma may rarely present as a mass occurring at the corneoscleral limbus. Therefore it should be considered in the differential diagnosis of any corneoscleral limbal mass lesion, particularly in children. Most are isolated lesions without systemic involvement which are treated by simple excision. But association with NF1 is possible and in that case screening for hematological malignancies is recommended.
Subject(s)
Corneal Diseases/pathology , Limbus Corneae/pathology , Scleral Diseases/pathology , Xanthogranuloma, Juvenile/pathology , Betamethasone/administration & dosage , Child, Preschool , Combined Modality Therapy , Corneal Diseases/therapy , Female , Glucocorticoids/administration & dosage , Humans , Infant , Male , Ophthalmologic Surgical Procedures , Prednisolone/administration & dosage , Scleral Diseases/therapy , Xanthogranuloma, Juvenile/therapyABSTRACT
PURPOSE: Filtration failure due to excessive postoperative scarring remains a major problem after glaucoma surgery. The authors have investigated whether glaucoma and filtration surgery are associated with increased levels of vascular endothelial growth factor (VEGF), and whether a humanized monoclonal antibody against VEGF, bevacizumab, can reduce postoperative scar formation and improve surgical outcome. METHODS: The levels of VEGF in samples of aqueous humor were measured by ELISA. The expression of the VEGF receptors Flt-1 and KDR was analyzed in cultured Tenon fibroblasts by real-time RT-PCR and Western blotting. The effect of VEGF and bevacizumab on Tenon fibroblasts in vitro was determined using a proliferation assay. The in vivo effect of the antibody was investigated in a rabbit model of trabeculectomy by measuring the intraocular pressure (IOP) and bleb area, and by immunohistological analysis of angiogenesis, inflammation, and fibrosis. RESULTS: VEGF levels were increased significantly in the aqueous humor of glaucoma patients and rabbits that had undergone surgery. Both VEGF receptors were expressed on Tenon fibroblasts. Fibroblast proliferation in vitro was stimulated by delivery of VEGF, and was inhibited by administration of bevacizumab. The antibody also reduced angiogenesis and collagen deposition significantly, and improved the outcome of glaucoma surgery in rabbits. CONCLUSIONS: VEGF was upregulated in the aqueous humor of glaucoma patients and in the rabbit model, and it stimulated fibroblast proliferation in vitro. This suggests that it is involved in the scarring process after filtration surgery. Bevacizumab reduced the proliferation of fibroblasts in vitro and improved surgical outcome.
Subject(s)
Cicatrix/prevention & control , Conjunctival Diseases/prevention & control , Glaucoma, Open-Angle/surgery , Postoperative Complications , Trabeculectomy , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Angiogenesis Inhibitors/administration & dosage , Animals , Anterior Chamber , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Humanized , Aqueous Humor/metabolism , Bevacizumab , Cell Proliferation/drug effects , Cells, Cultured , Cicatrix/etiology , Cicatrix/metabolism , Conjunctival Diseases/etiology , Conjunctival Diseases/metabolism , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Female , Fibroblasts/metabolism , Humans , Injections , Intraocular Pressure , Rabbits , Receptors, Vascular Endothelial Growth Factor/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tonometry, Ocular , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor Receptor-1/genetics , Vascular Endothelial Growth Factor Receptor-1/metabolism , Vascular Endothelial Growth Factor Receptor-2/genetics , Vascular Endothelial Growth Factor Receptor-2/metabolismABSTRACT
Biological functions of proteins are influenced by posttranslational modifications such as on/off switching by phosphorylation and modulation by glycosylation. Proteolytic processing regulates cytokine and chemokine activities. In this study, we report that natural posttranslational citrullination or deimination alters the biological activities of the neutrophil chemoattractant and angiogenic cytokine CXCL8/interleukin-8 (IL-8). Citrullination of arginine in position 5 was discovered on 14% of natural leukocyte-derived CXCL8(1-77), generating CXCL8(1-77)Cit(5). Peptidylarginine deiminase (PAD) is known to citrullinate structural proteins, and it may initiate autoimmune diseases. PAD efficiently and site-specifically citrullinated CXCL5, CXCL8, CCL17, CCL26, but not IL-1beta. In comparison with CXCL8(1-77), CXCL8(1-77)Cit(5) had reduced affinity for glycosaminoglycans and induced less CXCR2-dependent calcium signaling and extracellular signal-regulated kinase 1/2 phosphorylation. In contrast to CXCL8(1-77), CXCL8(1-77)Cit(5) was resistant to thrombin- or plasmin-dependent potentiation into CXCL8(6-77). Upon intraperitoneal injection, CXCL8(6-77) was a more potent inducer of neutrophil extravasation compared with CXCL8(1-77). Despite its retained chemotactic activity in vitro, CXCL8(1-77)Cit(5) was unable to attract neutrophils to the peritoneum. Finally, in the rabbit cornea angiogenesis assay, the equally potent CXCL8(1-77) and CXCL8(1-77)Cit(5) were less efficient angiogenic molecules than CXCL8(6-77). This study shows that PAD citrullinates the chemokine CXCL8, and thus may dampen neutrophil extravasation during acute or chronic inflammation.
