Biomedical subjects

Matthias D Becker

Publications and source records attributed to Matthias D Becker.

7 recordsLinked to original sources

PubMed2006

Interferon therapy for ocular disease.

PURPOSE OF REVIEW: Interferons were first known for their antiviral action. Immunomodulatory therapy with interferons has been studied in various diseases. This paper summarizes the role and presumed mechanisms of action of type 1 interferons in the treatment of ocular disease. RECENT FINDINGS: Preliminary data show beneficial effects of interferons in ocular disease such as Behçet disease and multiple sclerosis-associated uveitis in terms of visual acuity, intraocular inflammation activity, and chronic macular edema. Another mode of application is topical as an adjuvant treatment in viral keratitis or ocular surface malignancies. SUMMARY: Interferons are gaining a place in the treatment of ocular disease. Evidence is growing of their potential in ocular Behçet disease and multiple sclerosis-associated uveitis. Randomized, controlled clinical trials are needed to confirm this observation. Further insights into the complex mechanisms of action of interferons in health and disease will increase understanding of their mechanisms of action as a therapeutic substance.

Antineoplastic Agents↗

PubMed2005

A locus on chromosome 9p predisposes to a specific disease manifestation, acute anterior uveitis, in ankylosing spondylitis, a genetically complex, multisystem, inflammatory disease.

OBJECTIVE: Uveitis or intraocular inflammation is a major cause of visual loss. Acute anterior uveitis (AAU) affects approximately 40% of patients with ankylosing spondylitis (AS) but also affects patients with no evidence of spondylarthritis. We sought to determine whether a unique genetic region could be implicated in a specific manifestation-AAU-of a multisystem, inflammatory, genetically complex disease, AS. METHODS: Individuals from families multiplex for AAU were genotyped at 400 markers representing the ABI PRISM linkage map MD-10, and at the HLA-B, DRB1, DQA1, DQB1, and DPB1 alleles. Among the family members with AAU, 76 affected sibpairs were analyzed (6 without concomitant AS, 12 discordant for AS, and 58 concordant for AS). Two-point and multipoint nonparametric linkage analyses were performed, and 1-parameter allele-sharing model logarithm of odds (LOD) scores were determined. RESULTS: As previously reported for AS, linkage at the major histocompatibility complex region (chromosome 6p21) was evident, exhibiting the highest multipoint LOD score (4.96 at marker HLA-B). Strong linkage was seen at a region on chromosome 9p21-9p24, with a LOD score of 3.72 at marker D9S157. When compared with a companion cohort of AS families, the linkage at this region was found in association with AAU but not with AS. A third region on chromosome 1q23-1q31 was observed to have suggestive linkage (LOD 2.05 at marker D1S238), which overlaps with a region associated with AS. CONCLUSION: This is the first study in which a genetic region for AAU has been identified by genome-wide scan. Even though AS was highly prevalent in this cohort of families, a locus at chromosome 9p21-9p24 was identified that uniquely associates with AAU. Identifying the genetic perturbation at this region may advance our understanding of the mechanisms involved in tissue-specific pathology of complex inflammatory diseases.

Acute Disease↗

PubMed2005

Celecoxib, a selective inhibitor of cyclooxygenase 2 for therapy of diffuse anterior scleritis.

PURPOSE: Scleritis is a painful inflammation of the sclera that is often difficult to treat. Oral nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective. Results of treating 24 cases of diffuse anterior scleritis with the novel selective COX-2 inhibitor celecoxib are reported. DESIGN: Nonrandomized prospective study. METHODS: Twenty-four patients suffering from diffuse anterior scleritis were seen in the Interdisciplinary Uveitis Center in Heidelberg between April 2001 and April 2003. All patients were treated with a 200- to-800 mg dose of celecoxib per day, in divided doses, depending on the degree of discomfort and clinical severity. RESULTS: Twenty-two patients experienced significant clinical improvement within an average of 5 days of starting celecoxib. These patients reported a complete loss of pain and scleral redness. As they experienced complete symptomatic remission, the dose of celecoxib was tapered. Three of these patients suffered from a second attack of scleritis, with one patient requiring long-term low-dose therapy, one patient showing a nodular form, and the third showing no improvement. Treatment with celecoxib was associated with no side effects apart from allergic exanthema in two patients. CONCLUSION: Due to its anti-inflammatory potency and low rate of side effects, celecoxib is an effective drug for the treatment of diffuse anterior scleritis. Compared with other NSAIDs it shows minimal gastrointestinal side effects, so its high cost is justified. It represents an alternative drug therapy before systemic immunosuppressive treatment.

Adult↗

PubMed2005

Management of sight-threatening uveitis: new therapeutic options.

Over the past 2 decades therapy for the treatment of intraocular inflammation (uveitis) has developed into a highly differentiated approach with an increasing number of drug options. This paper primarily summarises literature from the past 5 years (2000 to May 2004), gives an update on systemic immunosuppressive therapy for non-infectious uveitis and speculates about new developments that could become relevant in the near future for the treatment of uveitis patients. The spectrum of immunosuppressive drugs has been notably expanded by tumor necrosis factor inhibitors, but with some limitations to uveitis. Behcet's disease is an example of uveitis where a multisystem disorder can affect the eye very severely. This clinical example has been used to investigate the utility of many different types of immunosuppressive therapies and the clinical approach is extensively discussed in this review. An accompanying table summarises the proposed mode of action, standard dosage, common adverse effects, as well as estimated cost of current treatment options.

Adrenal Cortex Hormones↗

PubMed2003

Immunohistology of antigen-presenting cells in vivo: a novel method for serial observation of fluorescently labeled cells.

PURPOSE: Dendritic cells and macrophages are phagocytic antigen-presenting cells that bridge the innate and acquired immune systems. The coexistence of subtypes of dendritic cells and macrophages with overlapping properties complicates resolution of their precise roles in an immune response within a given tissue. This report documents a method to identify and observe these cells over time in a living animal and thereby to visualize them during a dynamic immune response. METHODS: To label potential antigen-presenting cells, fluorescently tagged ovalbumin was injected into the anterior chambers of mouse eyes. Fluorescently tagged antibodies to cell surface proteins were injected to label specific cell types. Intravital fluorescence microscopy with digital image recording was used to visualize the labeled cells in the irises at various times after the injection. RESULTS: The pattern and density (116-148 cells/mm(2)) of cells labeled in vivo by fluorescent ovalbumin or F4/80 antibodies were similar to that identified by conventional wholemount immunostaining for macrophages and dendritic cells. Fluorescent antibodies specific for CD11b, CD11c, CD80, CD86, or major histocompatibility complex (MHC) class II protein each labeled selective populations of cells in vivo. In contrast to conventional histology, in vivo immunohistology permitted serial observations. The phenotype of cells labeled by fluorescent ovalbumin was not the same at 6 (95% CD11c(+)) and 24 hours (24% CD11c(+)) after injection. CONCLUSIONS: This method of in vivo immunohistology provides a tool for studying cell kinetics and dynamic interactions that cannot be assessed by conventional immunohistology. Furthermore, it avoids potential artifacts from tissue fixation and may work with antibodies that label cells poorly in vitro.

Animals↗

PubMed2002

Immune mechanisms in uveitis. What can be learned from in vivo imaging?

In many aspects, in vivo imaging is superior to other techniques, such as conventional histology, because it allows the stepwise process of leukocyte migration to be dissected. The potential uses of the in vivo imaging techniques have yet to be achieved. The transfer of lymphocytes with fluorescent dyes can be marked. APCs that ingest fluorescent antigen and use fluorescent antibodies specifically to label different types of APCs in the anterior segment can be identified. Combining these techniques could result in more exciting insights into uveitis and the mechanisms of the immune system. For example, one can confidently expect to be able to observe the extravasation of CFSE-marked DO11.10 T cells and their subsequent interaction with APCs containing red fluorescent OVA. The use of green fluorescent protein to measure the expression of various proteins has occurred in a variety of in vitro and in vivo models. To identify activated T cells specifically, heterozygous knock-in mice have been generated that have a cDNA for enhanced green fluorescent protein substituted for the IL-2 coding region on one allele [91]. Activated T cells from these IL-2-green fluorescent protein mice up-regulate the expression of the IL-2 gene and consequently synthesize the green fluorescent protein marker. The authors recently demonstrated the presence of these activated cells in vivo in the mouse iris [16]. With both the green fluorescent protein and the brighter yellow fluorescent protein the authors anticipate being able to detect in vivo the expression of various cytokines, such as IL-2, the Th1 cytokine IFN-gamma, or the Th2 cytokine IL-4, in T cells infiltrating the eye. First steps have been undertaken to establish in vivo imaging in human eyes. Toxicity of fluorescent dyes currently used for animal research and movement artifacts of the tissue under investigation amplified by the high magnification necessary for cell research, however, remain the major challenges to study leukocyte migration in human uveitis.

Antigen-Presenting Cells↗

PubMedDate not supplied

Long-term follow-up of patients with birdshot retinochoroidopathy treated with systemic immunosuppression.

PURPOSE: Birdshot retinochoroidopathy (BRC) is a rare uveitis syndrome of presumed autoimmune etiology. Therapy with systemic and periocular corticosteroids is of inconsistent efficacy, attendant with numerous potential long-term side effects. Corticosteroid-sparing strategies with agents such as cyclosporine A or azathioprine have been suggested for this disease. METHODS: We retrospectively reviewed the medical charts of patients with BRC who were evaluated consecutively at a tertiary-care, referral-based North American uveitis clinic over a 15-year period. RESULTS: Eleven Caucasian patients (22 eyes) were diagnosed with BRC, representing approximately 1% of all cases seen at the uveitis clinic. HLA-A29 was positive in all 11 patients. We elected to treat five patients with azathioprine, methotrexate, cyclosporine A, mycophenolate mofetil, and/or IvIg, as well as systemic or periocular corticosteroid injections. The median period of follow-up for the five treated patients was six years (range: 8 months-13 years). Inflammation was reduced or stabilized in five of five patients. CONCLUSION: Although the definitive strategy for the management of BRC is unknown, control of intraocular inflammation and preservation of vision is possible with corticosteroid-sparing immunosuppressive agents.

Adult↗