Lens dislocation in Marfan syndrome and UV-B light exposure.
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Eye Protective Devices↗
Biomedical subjects
Denis Wakefield
Publications and source records attributed to Denis Wakefield.
The role of ultraviolet irradiation and heparin-binding epidermal growth factor-like growth factor in the pathogenesis of pterygium.
Ultraviolet (UV) light is one of the major factors implicated in the pathogenesis of pterygium. The mechanism by which UV light induces this disease remains elusive. The aim of this study was to evaluate the effects of UVB irradiation on the expression of growth factors in cultured pterygium epithelial cells and to demonstrate their distribution within pterygium. We cultured pterygial epithelial cells from pterygium explants and these cells were exposed to 20 mJ/cm(2) of UVB. Total RNA was extracted at 0, 6, and 12 hours after irradiation. (32)P-labeled cDNA was synthesized and analyzed using microarray technology to determine the differential expression of 268 growth factor and cytokine related genes. Semiquantitative reverse transcriptase-polymerase chain reaction was used to corroborate this data. Conditioned media derived from cells exposed to UVB irradiation was analyzed for protein expression by enzyme-linked immunosorbent assay. Immunohistochemistry was used to evaluate the distribution of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in pterygium tissue. Analysis of the hybridization signals revealed that the genes encoding HB-EGF, fibroblast growth factor 3, and cytotoxic trail ligand receptor were consistently elevated at 6 and 12 hours after UVB treatment. HB-EGF mRNA was elevated 6.8-fold at 6 hours after irradiation and was augmented in culture supernatants after the same treatment. Furthermore, HB-EGF reactivity was identified in the epithelium and vasculature of pterygium by immunohistochemistry. HB-EGF was present in normal limbal epithelium, although it was not induced in cultured limbal epithelial cells by UV irradiation. HB-EGF is a potent mitogen, localized in pterygium tissue, and significantly induced by UVB in pterygium-derived epithelial cells. We postulate that this growth factor is a major driving force in the development of pterygia and a means by which UV irradiation causes the pathogenesis of pterygium.
Cell Culture Techniques↗
Regulation of MMPs and TIMPs by IL-1beta during corneal ulceration and infection.
PURPOSE: This study was conducted to investigate the role of IL-1beta in the regulation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in a mouse model of experimental keratitis and corneal injury. METHODS: Mice were injected subconjunctivally with 10 micro g of anti-mouse IL-1beta antibody 2 hours before challenge with Pseudomonas aeruginosa (strain 6294). Control animals received an equal volume and concentration of isotype control antibody at the same time. Eyes were enucleated at 0, 8, 24, and 72 hours, after bacterial challenge and processed for histologic examination. Some eyes were homogenized and used to evaluate production of MMP-2, MMP-9, TIMP-1, and TIMP-2 protein, by zymography and reverse zymography. RESULTS: Injury without bacterial infection resulted in increases in both MMP-2 and -9 and a slight but significant downregulation of TIMP-1. Administration of anti-IL-1beta just before injury and without bacterial infection resulted in a significant reduction in expression of MMP-2 (at 8 hours), MMP-9 (at 8 hours), TIMP-1 (at 8 and 72 hours), and TIMP-2 (at 8 hours). Mice treated with anti-IL-1beta antibody, before bacterial challenge, demonstrated markedly reduced corneal damage compared with the severe corneal injury and massive neutrophil infiltration observed in infected mice treated with control antibody. Administration of the neutralizing anti-IL-1beta antibody resulted in a significant reduction of MMP-9 and a change in the time course of TIMP-1 and -2 expression. The reduction in MMP-9 by anti-IL-1beta during infection was much greater than the reduction without infection. CONCLUSIONS: The results imply that IL-1beta has a central role in corneal destruction during bacterial keratitis and suggests that targeting IL-1beta may be a novel therapeutic strategy for microbial keratitis.
Animals↗
Uveitis: a global perspective.
PURPOSE: To study the patterns of uveitis in various geographic regions. METHODS: A systematic literature review was performed using the MEDLINE database, from 1966 to present. Studies that satisfied our described selection criteria were analyzed to provide a global perspective on uveitis. RESULTS: Twenty-two studies, which were the best available representatives of Australia, North and South America, Europe, Asia, and Africa, were included in the final analysis. The distribution of uveitis cases according to the anatomical site of inflammation in the various regions, and the causes and clinical disease associations of anterior, intermediate, posterior, and pan-uveitis were studied for each of the regions and a comparative analysis was performed. CONCLUSIONS: There are similarities and distinct differences in the patterns of uveitis in the various geographic regions. Such patterns of uveitis are influenced by combinations of geographical, environmental, and genetic factors.
Demography↗
Web-based self-assessments in pathology with Questionmark Perception.
Formative assessment with appropriate feedback is an effective method of promoting learning. Software tools are now available to facilitate the delivery of formative self-assessments via the World Wide Web. For the past 5 years, we have offered on-line formative self-assessments in pathology to undergraduate medical students. These assessments, which have been authored using Questionmark Perception, have proved particularly popular and have received high ratings in course evaluation surveys. Furthermore, they appear to have been effective in promoting student learning, with evidence that students made a genuine attempt to answer the questions in the assessment and that they learnt from doing so. The potential of on-line formative self-assessments for postgraduate training and continuing education in pathology so far remains untapped.
Computer-Assisted Instruction↗
Lens dislocation in Marfan syndrome: potential role of matrix metalloproteinases in fibrillin degradation.
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Adult↗
UVB-mediated induction of interleukin-6 and -8 in pterygia and cultured human pterygium epithelial cells.
PURPOSE: Pterygia are common ocular surface lesions that are thought to be induced by exposure to ultraviolet (UV) radiation. The hypothesis tested in the current study is that UV radiation modulates the expression of interleukin (IL)-6 and -8, which could promote the neovascularization and chronic inflammation regularly observed in pterygia. METHODS: Immunohistochemical analysis was performed on 10 pterygia and 14 specimens of normal conjunctiva (4 of which contained limbus), to identify the cellular source of these cytokines. Pterygium epithelial cells were exposed to UVB (0-100 mJ/cm(2)) and the expression of cytokine mRNA and protein was determined by reverse transcription-polymerase chain reaction (RT-PCR), RNase protection assay (RPA), and enzyme immunoassay. Similarly, pterygium tissue in organ culture was UVB irradiated and the supernatants analyzed for cytokine production. RESULTS: IL-6 and -8 proteins were abundantly expressed, predominantly by the pterygium epithelium, with additional IL-8 immunoreactivity associated with the vascular endothelium. In contrast, significantly less staining for both cytokines was observed in normal conjunctiva, cornea, and limbus. Expression of both IL-6 and -8 mRNA and protein was induced in UVB-irradiated pterygium epithelial cells in a time- and dose-dependent manner. Similarly, IL-6 and -8 proteins were significantly elevated in UVB-treated compared with nonirradiated pterygia. CONCLUSIONS: This study provides the first direct experimental evidence that implicates UV in the pathogenesis of pterygia. The two proinflammatory cytokines that are induced by UV radiation may play a key role in the development of pterygia, by initiating blood vessel formation, cellular proliferation, tissue invasion, and inflammation. Strategies aimed at reducing ocular exposure to UV light may decrease the incidence and recurrence of pterygia.
Cells, Cultured↗