6 results on '"Tamm, Ernst R."'
Search Results
2. Biological aspects of axonal damage in glaucoma: A brief review
- Author
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Tamm, Ernst R, Ethier, C Ross, Participants, The Lasker IRRF Initiative on Astrocytes and Glaucomatous Neurodegeneration, Dowling, John E, Downs, Crawford, Ellisman, Mark H, Fisher, Steven, Fortune, Brad, Fruttiger, Marcus, Jakobs, Tatjana, Lewis, Geoffrey, Masland, Richard H, Mitchell, Claire H, Morrison, John, Sharma, Sansar C, Sigal, Ian, Sofroniew, Michael, Wang, Lin, Wiggs, Janey, and Wu, Samuel
- Subjects
Biomedical and Clinical Sciences ,Ophthalmology and Optometry ,Neurodegenerative ,Neurosciences ,Eye Disease and Disorders of Vision ,Aging ,Aetiology ,2.1 Biological and endogenous factors ,Eye ,Neurological ,Animals ,Astrocytes ,Axons ,Glaucoma ,Gliosis ,Humans ,Intracranial Pressure ,Intraocular Pressure ,Nerve Degeneration ,Optic Disk ,Optic Nerve Diseases ,Lasker/IRRF Initiative on Astrocytes and Glaucomatous Neurodegeneration Participants ,Medical Biochemistry and Metabolomics ,Opthalmology and Optometry ,Ophthalmology & Optometry ,Ophthalmology and optometry - Abstract
Intraocular pressure (IOP) is a critical risk factor in glaucoma, and the available evidence derived from experimental studies in primates and rodents strongly indicates that the site of IOP-induced axonal damage in glaucoma is at the optic nerve head (ONH). However, the mechanisms that cause IOP-induced damage at the ONH are far from understood. A possible sequence of events could originate with IOP-induced stress in the ONH connective tissue elements (peripapillary sclera, scleral canal and lamina cribrosa) that leads to an increase in biomechanical strain. In consequence, molecular signaling cascades might be activated that result in extracellular matrix turnover of the peripapillary sclera, changing its biomechanical properties. Peripapillary sclera strain might induce reactive changes in ONH astrocytes and cause astrogliosis. The biological changes that are associated with ONH astrocyte reactivity could lead to withdrawal of trophic or metabolic support for optic nerve axons and cause their degeneration. Alternatively, the expression of neurotoxic molecules might be induced. Unfortunately, direct experimental in vivo evidence for these or other scenarios is currently lacking. The pathogenic processes that cause axonal degeneration at the ONH in glaucoma need to be identified before any regenerative therapy is likely to succeed. Several topics and emerging techniques should be pursued to enhance our understanding of the mechanisms that are behind axonal degeneration. Among them are: Advanced imaging techniques, the development of in vivo markers to identify axonal injury, the generation of molecular approaches for in vivo detection of mechanosensitivity and for molecular manipulation of the ONH, a more complete characterization of retinal ganglion cells, the use of organ cultures, 3D-bioprinting, and the engineering of microdevices that can measure pressure. Questions that need to be answered relate to the specific roles of astrogliosis, neuroinflammation, blood flow and intracranial pressure in axonal degeneration at the ONH.
- Published
- 2017
3. Ligand-functionalized nanoparticles target endothelial cells in retinal capillaries after systemic application
- Author
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Pollinger, Klaus, Hennig, Robert, Ohlmann, Andreas, Fuchshofer, Rudolf, Wenzel, Rebecca, Breunig, Miriam, Tessmar, Joerg, Tamm, Ernst R., and Goepferich, Achim
- Published
- 2013
4. The role of TGF-β in the pathogenesis of primary open-angle glaucoma
- Author
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Fuchshofer, Rudolf and Tamm, Ernst R.
- Published
- 2012
- Full Text
- View/download PDF
5. Biological aspects of axonal damage in glaucoma: a brief review (1)
- Author
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Tamm, Ernst R. and Ethier, C. Ross
- Subjects
genetic structures ,Intracranial Pressure ,Optic Disk ,Glaucoma ,eye diseases ,Article ,Axons ,nervous system ,Astrocytes ,Nerve Degeneration ,Optic Nerve Diseases ,Animals ,Humans ,sense organs ,Gliosis ,Intraocular Pressure - Abstract
Intraocular pressure (IOP) is a critical risk factor in glaucoma, and the available evidence derived from experimental studies in primates and rodents strongly indicates that the site of IOP-induced axonal damage in glaucoma is at the optic nerve head (ONH). However, the mechanisms that cause IOP-induced damage at the ONH are far from understood. A possible sequence of events could originate with IOP-induced stress in the ONH connective tissue elements (peripapillary sclera, scleral canal and lamina cribrosa) that leads to an increase in biomechanical strain. In consequence, molecular signaling cascades might be activated that result in extracellular matrix turnover of the peripapillary sclera, changing its biomechanical properties. Peripapillary sclera strain might induce reactive changes in ONH astrocytes and cause astrogliosis. The biological changes that are associated with ONH astrocyte reactivity could lead to withdrawal of trophic or metabolic support for optic nerve axons and cause their degeneration. Alternatively, the expression of neurotoxic molecules might be induced. Unfortunately, direct experimental in vivo evidence for these or other scenarios is currently lacking. The pathogenic processes that cause axonal degeneration at the ONH in glaucoma need to be identified before any regenerative therapy is likely to succeed. Several topics and emerging techniques should be pursued to enhance our understanding of the mechanisms that are behind axonal degeneration. Among them are: Advanced imaging techniques, the development of in vivo markers to identify axonal injury, the generation of molecular approaches for in vivo detection of mechanosensitivity and for molecular manipulation of the ONH, a more complete characterization of retinal ganglion cells, the use of organ cultures, 3D-bioprinting, and the engineering of microdevices that can measure pressure. Questions that need to be answered relate to the specific roles of astrogliosis, neuroinflammation, blood flow and intracranial pressure in axonal degeneration at the ONH.
- Published
- 2017
6. Regulation of human myocilin/TIGR gene transcription in trabecular meshwork cells and astrocytes: role of upstream stimulatory factor.
- Author
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Kirstein, Lucienne, Cvekl, Ales, Chauhan, Bharesh K., and Tamm, Ernst R.
- Subjects
GENETIC transcription ,GLUCOCORTICOIDS ,PROTEINS ,ASTROCYTES ,DNA - Abstract
Background: Mutations in the myocilin (MYOC)/TIGR gene are responsible for autosomal-dominant juvenile primary open-angle glaucoma (POAG). In patients with non-autosomal-dominant POAG, such mutations are rare, but the expression of MYOC/TIGR in the trabecular meshwork (TM) of the eye is considerably higher than in normals. We performed transfection, DNAse I footprinting, mutagenesis and electrophoretic mobility shift assays (EMSA) to identify elements responsible for the basal transcription of MYOC/TIGR in TM cells and astrocytes. Results: DNAse I footprinting experiments of the human MYOC/TIGR promoter showed a major protected area between nt -106 to -77, which was not conserved in the homologous region of the mouse myoc/tigr promoter. In addition, the TATA-box was protected, as well as at least three downstream sites, including an AP-1-like sequence. Deletion of the -106 to -77 region caused a substantial loss of functional promotor activity in all cell types. Site-directed mutagenesis and EMSA experiments revealed the presence of two regulatory elements in the -106 to -77 region. Each of these cis-elements is essential for minimal promoter activity. The 5′-half of the region contains a sequence with similarities to NF-κB-related sites, however, binding of NF-κB could not be confirmed by EMSA. The 3′-half contains a canonical E-box sequence. EMSA experiments showed that the upstream regulatory factor (USF) was binding to the E-box sequence and that the binding can be supershifted by specific antibodies. Conclusions: Several DNA-protein binding elements contribute to a transcription of MYOC/TIGR, and USF is critically required for its basal transcription in trabecular meshwork cells and astrocytes. [ABSTRACT FROM AUTHOR]
- Published
- 2000
- Full Text
- View/download PDF
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